WO2010086862A1 - Comprehensive electronic laboratory notebook - Google Patents

Comprehensive electronic laboratory notebook Download PDF

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Publication number
WO2010086862A1
WO2010086862A1 PCT/IL2010/000082 IL2010000082W WO2010086862A1 WO 2010086862 A1 WO2010086862 A1 WO 2010086862A1 IL 2010000082 W IL2010000082 W IL 2010000082W WO 2010086862 A1 WO2010086862 A1 WO 2010086862A1
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Prior art keywords
experimental
database
data
experiment
laboratory notebook
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PCT/IL2010/000082
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French (fr)
Inventor
Roi Paz
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Sparklix Ltd.
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Publication date
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Publication of WO2010086862A1 publication Critical patent/WO2010086862A1/en

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    • GPHYSICS
    • G06COMPUTING; CALCULATING OR COUNTING
    • G06QINFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR ADMINISTRATIVE, COMMERCIAL, FINANCIAL, MANAGERIAL OR SUPERVISORY PURPOSES; SYSTEMS OR METHODS SPECIALLY ADAPTED FOR ADMINISTRATIVE, COMMERCIAL, FINANCIAL, MANAGERIAL OR SUPERVISORY PURPOSES, NOT OTHERWISE PROVIDED FOR
    • G06Q10/00Administration; Management

Definitions

  • the invention generally relates to the field of Laboratory Information Management Systems (LIMS). More specifically, the invention relates to computer-implemented electronic laboratory notebooks (ELNs), for recording, retrieving and analyzing scientific experimental data.
  • LIMS Laboratory Information Management Systems
  • ENNs computer-implemented electronic laboratory notebooks
  • a laboratory notebook aims to permanently record what was done on a project and acts as proof of experiments performed.
  • the laboratory notebook has to provide a complete record of activities in a way that allows co-workers to repeat experiments and obtain the same results without having support from the original author.
  • the records in the laboratory notebook should include the object of the investigation, the experimental or theoretical background, a description of the experiment and its parameters, and the experimental results.
  • the tool should allow a scientist to easily group and retrieve any experiments having a common denominator, which allows instant recall and comparison of similar topics which he has previously studied, even over a period of years. Often, a scientist will upgrade his personal computer, and not retain hard copies of graphs or experimental data which he feels is unimportant, only to regret this years later when he wishes to return to study the topic once again.
  • ENNs electronic laboratory notebooks
  • U.S. Pat. Publication 2004/0015514 to Melton et al. U.S. Pat. No.
  • data object used in relation to laboratory research data objects, refers to any details of experiments planned or performed. These include, but are not limited to, the details of reagents, samples, concentrations, protocols, results, bioinformatic results, genetic or protein sequences.
  • data object as used in the invention additionally includes budget details, inventory lists, user specifics, schedules for performance of tasks .
  • An electronic laboratory notebook system comprising: computer associated peripherals; a processor configured to interact with the peripherals, by: a)storing a plurality of data objects pertaining to laboratory experiments, in at least one database, the storing performed using data object placement logic, and the data objects are associated with metadata tags; and b) retrieving data objects using metadata logic for retrieval.
  • the processor is configured to output a pictorial image of experimental samples of a predetermined experiment, wherein the experimental samples are stored as data objects in the database, hi such case, in some embodiments the outputted pictorial image of experimental samples includes the concentration of reagents in the sample, and includes the location of the sample within a plurality of samples.
  • the database is selected from at least one of the following types: a relational database, a key/value database, and a modified relational database.
  • the data objects in the database are related hierarchically, wherein the first level of hierarchy is an experiments table, the second level of hierarchy is an experimental design table including a list of experimental samples, the third level of hierarchy is a quantity and concentration table, the forth level of hierarchy is a protocol table, and the fifth level of hierarchy is a results table.
  • the database may comprise a table of inventory of consumable materials. In such case, data flow may occur between data objects in the inventory table and between associated objects stored in the database in an experimental design table.
  • the database optionally comprises a budget planning table. Optionally, data flow occurs between data objects in the budget planning table, and between associated objects stored in the database in an experimental design table.
  • the processor is configured to perform one or more of the following functions: output a pictorial image of dilutions included in an experiment, and to calculate reagent concentrations.
  • the processor is configured to perform one or more of the following functions: calculate the cost of an experiment, compute and display a budget remaining, display an alternative reagent, and deplete reagents from inventory using data flow between an experimental design table and between an inventory table.
  • the processor may be configured to perform one or more of the following functions: perform a search of scientific literature using the Internet, send genetic or protein sequences to an external database, upload results from an analytical instrument, and provide a hyperlink for accessing a website providing a bioinformatic tool, store and retrieve data related to experimental research data, retrieve protocols for performance of experiments, display experimental results graphically, perform statistical analysis of experimental results, display inventory, share digital files with another second user at a remote location, schedule tasks to be performed using an analytical instrument, add an authentication to experimental data.
  • the system utilizes a server in communication with a remote processing device of a user, wherein the server is configured to perform steps a)-b) and to communicate with the remote processor of the user, using a graphical user interface.
  • the processor may be configured to automatically suggest inclusion of controls deemed to be standard controls in a specific experimental design. Additionally, the processor may be configured to identify experimental results deemed to be abnormal in comparison to previously obtained experimental results.
  • the processor may be configured to import experimental results from the controlling processor of an analytical instrument.
  • editing of the protocol table results in display of the edited protocol in a marked up fashion illustrating changes made to the protocol.
  • the invention additionally provides a computer-implemented method for planning a research experiment and recording experimental data, the method comprising the following steps: a) storing an experimental design including details of experimental samples, in a computer readable database; b) storing an experimental protocol associated with the experimental design; c) storing experimental results; d) allowing performance of statistical calculations of the experimental results.
  • the method may further comprise the step of outputting a pictorial image of the experimental samples.
  • the method further comprises the step of outputting a pictorial image of dilutions to be performed.
  • the method may further comprise the step of storing an inventory table in the database, wherein data flow occurs between objects included in the inventory table and between consumable materials listed in the protocol, and between the experimental samples, such that when an experiment is deemed to have occurred, the inventory table will automatically be depleted respectively.
  • the method comprises the step of detecting whether consumable materials included in the experimental protocol are present in an inventory table stored in the database, and alerting a user when the level of the consumable material falls below a predetermined level.
  • the method further comprises the step of entering a budget into the database, wherein data flow occurs between data objects in the budget, and between associated objects stored in an experimental design stored in the database.
  • the method may additionally comprise the step of scheduling a task on an analytical instrument necessary for the experimental protocol.
  • the method may further comprise one or more of the following steps: retrieving data related to experimental research data, retrieving a protocol for performance of an experiment, displaying experimental results graphically, performing statistical analysis of experimental results, displaying inventory, sharing digital files with another second user at a remote location, scheduling tasks to be performed using an analytical instrument, adding an authentication to experimental data, performing a search of scientific literature using the Internet, sending genetic or protein sequences to an external database, sending experimental data to a remote user, uploading analytical data from an analytical instrument, and accessing an external website providing bioinformatics analysis tools.
  • the method utilizes a server in communication with a remote processing device of a user, wherein the server is configured to perform steps a)-d) of the method, and to communicate with the remote processor of the user, using a graphical user interface.
  • the invention additionally provides computer readable storage medium comprising software capable of performing the method of the invention.
  • Fig. 1 illustrates central tabs provided by the user interface of the invention, including Home, Protocols, Experiments, Analysis, Templates, Inventory, Users and Google Docs.
  • Fig. 2 illustrates an Experimental Design interactive screen for planning an experiment.
  • Fig. 3 illustrates a pictorial image of a dilution to perform during an experiment, including reagent volumes and reagent concentrations. The image was outputted automatically after entering some of the dilution parameters.
  • Fig. 4 illustrates reagents included in an experiment in table form, and illustrates controls which may be added using an Add Control button.
  • Fig. 5 illustrates an experimental protocol screen.
  • Fig. 6 illustrates the volumes and concentrations of certain reagents included in an experiment, charted in table form.
  • Fig. 7 illustrates an inventory screen.
  • Fig. 8 illustrates a results screen, with results included in spreadsheet format.
  • Fig. 9 illustrates an experiments screen for retrieval of specific planned or executed experiments.
  • Fig. 1OA illustrates an additional screen for retrieval of specific planned or executed experiments, in which metadata keywords and filter level may be entered.
  • Fig. 1OB illustrates experiments retrieved during a search, shown in a list format and in a spreadsheet format for comparison of experimental results.
  • Fig. 11 illustrates a screen for handling genetic and protein sequences.
  • Figs. 12 and 13 illustrate template screens for design of a microwell plate.
  • Fig. 14 illustrate GoogleDocsTM functions for sharing files between users, for electronic chatting, and for performing statistical and comparative analysis of results.
  • Fig. 15 illustrates a cell count experiment charted using a data spreadsheet from a GoogleDocsTM tool.
  • Fig. 16 illustrates a budget planning screen.
  • Fig. 17 illustrates a task scheduling screen.
  • Fig. 18 illustrates a screen listing users with permission to access the system.
  • Figs. 19-22 describe screens allowing a user to performing a calculation relevant to several samples included in an experiment.
  • Fig. 23 is a flow chart illustrating the data flow and hierarchy of the modules that form the invention.
  • Fig. 24 is a diagram illustrating implementing the invention using a remote server, in a cloud computing environment. It will be appreciated that for simplicity and clarity of illustration, elements shown in the drawings have not necessarily been drawn accurately or to scale. Reference numerals may be repeated among the drawings to indicate corresponding or analogous elements. Moreover, some of the blocks depicted in the drawings may be combined into a single function.
  • the present invention provides a comprehensive Electronic Laboratory Notebook (ELN) which simplifies all aspects of running an active laboratory, from planning to execution of an experiment, and provides computational analysis of results, inventory management, budget planning, scheduling of tasks or instruments, sharing of experimental data between scientists at remote locations, posting new sequences to online biological databases, and performance of a scientific literature search.
  • ENN Electronic Laboratory Notebook
  • the invention additionally can be used to perform a bioinformatics search, which may include, for instance, use of software for statistical comparison of genetic or protein sequences, or access of genetic/protein databases such as GenBank or BLAST (both of the NCBI, belonging to National Institutes of Health (NIH), Bethesda MD).
  • GenBank or BLAST both of the NCBI, belonging to National Institutes of Health (NIH), Bethesda MD.
  • the invention may be used to obtain access to additional bioinformatics tools and advanced statistical tools.
  • the invention may be used to order materials, devices or products from appropriate vendors using the internet.
  • the ELN of the invention conforms to regulatory procedures by allowing digital signatures and time stamps to be added to documents.
  • the invention can instantaneously provide a pictorial version of the experimental samples and automatically calculate dilutions and concentrations, thus preventing miscalculations during experimental design, which can doom an entire week- long experiment. Automatic generation of such a visual aid has not been previously described in the art. Similarly, automatic calculation of dilutions and final concentrations is not known in the art.
  • Search results may include literature documents, links, bioinformatics results, and references to prior experiments or prior results.
  • Search results may include searching information obtained, keywords used, and their context or relation in the search (e.g. search at experiments, protocols, by users, etc.).
  • the ELN of the invention provides access to bioinformatics tools, chemoinformatics tools, statistical tools and allows searches of external database (e.g. for primer design, BLAST, for searching genome/protein databases, to design molecules, etc.).
  • GUI graphical user interface
  • TTI tabbed document interface
  • the initial screen depicted in Fig. 1 illustrates a list of the active tasks 10, active experiments 12 and active projects 14 entered by the scientist. A user may return to this initial screen by selecting the Home tab 100.
  • a specific active experiment 12 such as the "MG cond2" experiment 16
  • clicking on the "edit” icon 18 related to this experiment will open a new screen, illustrated in Fig. 2.
  • a user may choose to open a new experiment, which he may title as desired, and may continue to the screen described in relation to Fig. 2.
  • FIG. 2 at left, clicking upon Introduction 20 will allow editing of the Introduction related to a specific experiment.
  • a new editable window will open, allowing the scientist to type in any desired text, such as a description of the background, aim of the experiment, etc.
  • Graphical data, video or bioinformatics results may be added as well, as a visual aid, and all text will be saved and associated with the new experiment, which the scientist titles as he wishes.
  • Metadata describing the important aspects of the experiment may be added, and will aid in retrieval of experiments linked with a common denominator such as a common topic, common experimental technique, a specific individual performing the research, etc.
  • metadata which may aid in subsequent retrieval of specific experiments include: the title, subject, description, source, language, relation, coverage, name of user, date, type, format and identifier.
  • a user may click on buttons Add Reaction 24, Add Tube 26, or Add Plate 28. These allow recordation of new reactions, of additional related test-tubes, or of a new microwell plate.
  • Reagents which were previously entered by the user appear in table style, under the headings: Reagent 30, Quantity 32 and Final Concentration 34.
  • Each reagent entered may be edited, or removed, by clicking on Change 36 or on Remove 38.
  • New reagents may be added by clicking on Add Reagent 40 (bottom of Fig. 2).
  • the invention aids in performing mathematical calculations necessary for performance of most experiments, such as serial dilutions of reagents or reactants.
  • a visual image of the test-tubes and how to perform the dilution is presented to the user at the click of a button.
  • the first charted line 40 requires performance of 4 serial dilutions of Mg 100 mM. Clicking on Change 36 adjacent to the first line, opens a new window, shown in Fig. 3, which details the dilution and pictorially shows how to perform the dilution.
  • the software immediately calculates the amount of each reagent necessary to reach the proper dilution, and outputs a picture 50 of the microtubes and of the amount of each reagent per tube.
  • a pictorial depiction has not been previously available at the touch of a button. This prevents miscalculations and records the dilution process for future viewing.
  • a printout may be taken to the lab-bench, for easy reference during actual performance of the experiment, while records of the Experimental Design and chart of reagents used are retained in the system memory.
  • control microtubes may be added by clicking on Add Control 51 (at the bottom of Fig. 4).
  • Controls are saved to the system's memory in two manners: linked to the specific experiment, and saved by searchable keywords, for automatic retrieval when a new experiment is designed using a similar protocol.
  • the specific PCR experiment shown in Fig 4 includes a Negative Control 52 (without the DNA template), and a positive control 54, the system will cue the user in a future PCR experiment and will ask whether to include these or similar controls.
  • Protocols may include widely published laboratory technique protocols, such as molecular biology techniques published by Maniatis, et al., "Molecular Cloning; A Laboratory Manual” (Cold Spring Harbor Lab, New York, 1982. Alternatively, protocols may be those specifically developed or fine-tuned by the user or his colleagues.
  • Edit tab 59 may type in the changes, which will appear in Marked Up format (showing additions in underline), in conformity to FDA regulations.
  • Sign tab 61 may select the Sign tab 61, to add a digital authentication, date/time stamp, and seal the record from further editing.
  • samples 1-4 are charted in Table form, detailing the experiment itself, including a list of all reagents to be added, and including the concentration and quantity of each reagent. Samples are numbered.
  • the Inventory 600 tab is illustrated. Materials which were consumed in the experiment performed (best shown in Fig 2), will automatically be depleted from the Inventory, relative to the amount consumed. For instance, in this case, forward primer 60, PCR buffer 62, reverse primer 64, Taq DNA polymerase 66 are some of the materials used in the experiment shown in Fig. 2, and the amount consumed will be adjusted in the Inventory. Appropriate flags will appear onscreen to indicate to the user that a specific material is in danger of depletion and should be reordered.
  • the supplier information is available from the Supplier menu 68, and materials may be ordered online using a link to relevant suppliers.
  • the Material Type menu 70 lists materials by type (e.g. antibiotics, buffers, DNA templates, primers, culture mediums), and allows performance of an internal database search to detect materials of a similar nature.
  • results may be viewed by clicking on Results 72 (left bottom). This will open a new screen, described in relation to Fig. 8.
  • results 72 may be charted by typing them in manually into the spreadsheet 74. Analysis of results, including all typical spreadsheet computations may be made by selecting any of the dropdown menus 76 or buttons 80 of the spreadsheet, or by using widely known spreadsheet commands or shortcuts. The results may be presented in graph format.
  • results may be saved as Microsoft Office documents (Word, Excel), as photos, drawings, etc.
  • results may be imported directly from the instrument in which the experiment was performed by selecting the Add Document tab 82 (top left).
  • the software of the invention can interface with certain predetermined laboratory instruments which have controlling processors, to obtain the results of an experiment such as an experiment recently run. Results are uploaded to the properly linked database location. Virtually all modern analytical devices and instruments are operated by a controlling computer and accordingly experimental results are provided in electronic form. Though a research laboratory typically has many different such devices, which may originate in various manufactures, the ELN of the invention advantageously can seamlessly integrate the experimental data and results produced by some of these analytical devices and instruments, by means of an instrument interfacing module.
  • Non-limiting examples of instruments which one may envision interfacing with, include: an ELISA microplate reader, a PCR thermocycler, an HPLC system, a mass spectrometer, infrared thermography instruments, chromatography instruments, capillary electrophoresis instruments, optical reflection instruments, optical transmission instruments, viscometry instruments, mechanical resonators, solubility instruments, differential scanning calorimetry instruments, elongation instruments, indentation instruments, deformation or spectroscopy instruments.
  • instruments which one may envision interfacing with, include: an ELISA microplate reader, a PCR thermocycler, an HPLC system, a mass spectrometer, infrared thermography instruments, chromatography instruments, capillary electrophoresis instruments, optical reflection instruments, optical transmission instruments, viscometry instruments, mechanical resonators, solubility instruments, differential scanning calorimetry instruments, elongation instruments, indentation instruments, deformation or spectroscopy instruments.
  • the Experiments tab 300 has been selected, to search for and retrieve specific experiments that have been performed or are planned. Searching may be performed by entering metadata keywords in the Search For 84 field. Searching may optionally be according to the Date 86.
  • the Analysis tab 400 has been selected, to open the screen illustrated.
  • the user may select three fields 91 of metadata keywords to search through in order to retrieve one or several experiments saved in the database of the system.
  • the filter condition 93 may be selected as well, in order to fine-tune the search.
  • any relevant experiments will be retrieved from the database of the invention. Search results are shown in Fig. 1OB.
  • the search results obtained are illustrated in table format 97, which indicates the experiment title 99 and the relevancy levels 101 of the fields searched.
  • a user may press on the Create Spreadsheet button 103, to plot the experimental results from several experiments in a comparative spreadsheet 105, which may optionally be viewed as a plotted graph.
  • This allows analysis of experiments having related subject- matter. For instance, one may view how changing a specific parameter affected the results obtained, such as changing the cell source used, or changing the enzymes or reaction conditions.
  • One may view changes in results obtained in various timeframes (e.g. mature test animal vs. immature test animal).
  • Sequences 94 will open a new window for handling genetic and protein sequences, shown in Fig. 11.
  • genetic and protein sequences may be searched and viewed. Search may be based on the Accession 96 number issued to the sequence. The search may be performed either in the internal database of the invention, or in external genetic databases open to the public, such as Genbank (of the NCBI, belonging to National Institutes of Health (NIH), Bethesda MD). A new sequence file may be submitted to Genbank using the Upload Genbank File field 98.
  • Templates tab 500 has been selected, to open the screen shown for design of an experiment performed on a microwell plate.
  • the software identified two templates of microwell plates which can be used to design a new experiment, as shown in the list titled “2 Plate Templates Found” 102.
  • the user may select any of the buttons “New 6 well plate” 104, "New 24 well plate” 106, etc. Selection of "New 24 well plate” 106 opens the window shown in Fig. 13.
  • a 24-well plate is illustrated in pictorial form 108, which can be printed out for use at the lab bench during performance of the experiment.
  • User first enters sample groups 110 (T1-T3), and selects whether samples should be placed horizontally or vertically in the microwells.
  • the sample groups 110 are color-coded upon the pictorial form 108 of the microwell plate, for visual clarity during performance of the experiment.
  • a key for the color coding is provided adjacent to the picture image of the microwell plate, detailing which color is associated with which sample group.
  • the GoogleDocsTM tab 800 has been selected to allow a user to collaborate with research scientists at remote locations by sharing any files of interest using the Share button 112.
  • Clicking on the More Actions button 113 opens a chat option, so that a user may initiate an online dialog with a researcher at a remote location, to discuss for instance, a data chart they are both viewing simultaneously using the Share 112 option.
  • Clicking on the Search Templates button 114 allows access of tools provided by GoogleTM, such as Correlative Statistics, for additional data analysis opportunities.
  • Clicking on Show Search Options 115 will allow a user to perform an external search of scientific literature using the Internet, to reach for instance, PubMed or any other journal articles published online.
  • BLAST of the NCBI, belonging to National Institutes of Health (NIH), Bethesda MD
  • NAH National Institutes of Health
  • Bethesda MD National Institutes of Health
  • BLAST software additionally is available to design molecules, or primers.
  • the Search Options menu provides a hyperlink for accessing these or other bioinformatics tools.
  • a cell count experiment has been charted by opening a data spreadsheet using a GoogleDocsTM tool.
  • the chart may be edited, or may be sent to additional users.
  • the Home tab 100 has been selected, followed by Projects 116, to reach a budget-planning option.
  • Individual projects may be scheduled, and their budget entered in the fields Budget 118, and Current Budget 120.
  • the budget remaining will be adjusted accordingly.
  • the prices of consumable reagents used can be automatically obtained from the Inventory database by data flow, so that upon planning of the experiment the user will be made aware of the cost of the experiment planned.
  • task scheduling is available by clicking on Tasks 122 after selecting the Home tab 100. Dates may be entered in Start Date 124 or Due Date 126 fields, individual Assigned Users 128 may be entered, and after pressing the Save Task button 130, a screen will open to allow a user to schedule use of specific instruments, which are typically shared by multiple users.
  • Users tab 700 opens a screen listing which users are currently logged on. Selecting a specific user from the list will open a new screen indicating which files they have permission to access. Pressing the New User button 132 allows addition of new users.
  • Figs. 19 through Fig. 22 describe the instance in which a planned experiment entails performing a calculation which is relevant to several samples and the user wishes to establish a linkage between the calculation and between specific samples.
  • the Add Form button 134 may be pressed to open a new screen
  • the user wishes to generate a form, in which the optical density
  • OD OD obtained in a first measurement
  • OD2 OD2
  • the user may select the fields to relate as being "ODl” 136 and "OD2" 138, and then select the term formula 140 from the drop-down menu. After pressing the OK button 142, the next screen shown in Fig. 21 will open.
  • the field Sum 144 has been entered, and the field type Formula 146 and Return the Sum of all Numbers 148 have been selected from the wide variety of calculation options available in drop-down menu 150. Clicking on the Save Form button 152 will save this calculation.
  • This form will automatically become associated with the protocol used to perform this experiment, so that a user planning a similar experiment will be queried whether to include this calculation in the new experiment.
  • the ELN software of the invention is operable from any suitable computer, computer system or related group of computer systems known in the art.
  • the software is installed upon a server or server computer system which is connected by at least one input/output port to a communication network.
  • the communication network may be a local area network connecting a plurality of computers via any suitable networking protocol, including but not limited to Ethernet.
  • the communication network is the Internet and the system comprises server software capable of communicating with client computers via the Internet via any suitable protocol, including but not limited to HTTPS.
  • the invention may be provided to a user as software as a service (SaaS) which will obviate a user from hardware needs such as a server and necessary server maintenance, security, etc.
  • SaaS software as a service
  • a user may use a browser such as Internet ExplorerTM, Mozilla Firefox, Chrome or Safari, to browse on the server via the internet.
  • Any processing device may be utilized, including for instance, a personal computer, a laptop, a PDA or a cellular phone.
  • the invention is embodied in any suitable programming language or combination of programming languages, including Google Web Toolkit, JAVA, database managers and MySQL.
  • Each software component can be implemented in a high-level procedural or object- oriented programming language, or in assembly or machine language if desired.
  • the programming language may be a compiled or interpreted language.
  • a database which may be any suitable database for storing data objects and metadata relating thereto. Any suitable database program may be used.
  • the database is a relational database and a key/value database.
  • database is a modified relational database.
  • the search logic used for subsequent retrieval of experiments from the database is any suitable step, process, function or series of steps, processes and functions known in the art for searching a database.
  • Each workstation includes a graphical user interface (GUI). The contents of the screens, the functionality of the system and the work process may be adjustable to a user's needs.
  • GUI graphical user interface
  • the screen designs, terms and work process reflect the scientific field and are user- friendly since they display and interact with the user in syntax familiar to a life sciences research scientist. Thus use of the system appears intuitive.
  • the objects (interactive fields) in the ELN are updated in real time. In some embodiments, there is complete data flow between certain of the objects. In some embodiments, the objects are modular. Thus, the user can work with few or all of the objects of the invention according to his needs at a given time. The modularity allows integration with a variety of tools accessible on the Internet, using links provided by the invention.
  • the invention can be implemented using digital electronic circuitry, or in computer hardware, firmware, software, or in combinations of them.
  • a flow chart is shown, illustrating the data flow and hierarchy of the modules that form the invention.
  • Data may flow in both directions from modules depicted on the periphery of the flow chart (inventory, devices, samples, collaborators, project management, task management), towards, or out from, modules depicted at the center of the flowchart.
  • Inner modules represent central screens of the invention, pertaining to specific experiments planned or performed (introduction, experimental design, procedures, experiment comparison analysis, etc.).
  • the invention is implemented in cloud computing using a remote server.
  • Cloud computing refers to using a personal computer or PDA to to access a server running the software of the invention, via the internet.
  • the graphical interface of the application appears the same for all users and organizations, and uses the same database upon the server, however each user is identified according to the organization he is affiliated with, and can view only his secured data. Users can choose to share data with external users to the organization or to work in a collaborative space set aside for all users and organizations.
  • Suitable processors for implementation of the invention include, by way of example, both general and special purpose microprocessors.
  • a processor will receive instructions and data from a read-only memory and/or a random access memory.
  • a computer will include one or more mass storage devices for storing data files; such devices include magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and optical disks.
  • Storage devices suitable for tangibly embodying computer program instructions and data include all forms of non-volatile memory, including by way of example semiconductor memory devices, such as EPROM, EPROM, and flash memory devices; magnetic disks such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM disks.
  • the electronic lab notebook of the invention accommodates all aspects of conducting a laboratory, including planning and executing experiments, and recording and analysis of results.
  • the invention further allows on-demand bio-informatics, on-demand calculators, on-demand analysis, full integration of statistical tools, real time ERP (Enterprise Resource Planning), real time business intelligence (BI) and real time executive managers dashboard for summaries and control the organization and particular the lab resource.
  • ERP Enterprise Resource Planning
  • BI real time business intelligence
  • the software of the invention can learn. It is capable of identifying extreme deviations in the experimental results, and thus identifying and isolating potentially false results. It is dynamic in its ability to cope with user error during an experiment or to identify repeated failures such as extreme deviations obtained by different users, for example, as a result of a damaged component. Thus, the system reduces inaccuracies resulting from human errors.
  • the Electronic Laboratory Notebook (ELN) of the invention provides an extremely comprehensive tool for running an active research laboratory.
  • the invention provides previously unknown tools such as a pictorial image of samples and of dilutions to perform. This image may be printed out and taken to the lab bench during performance of the experiment. Another novel tool is automatic calculation of reagent concentrations, which prevents error in experimental design, thus vastly increasing repeatability of experiments.
  • the invention allows protocols to be retrieved at the touch of a button, allows computation and analysis of results, and allows sharing of experimental data between remote locations, which promotes scientific collaboration.
  • the software of the invention is saved upon a server accessible using the Internet, all data may be accessed from any location, allowing a visiting scientist access to data from his home laboratory.
  • the ELN of the invention is comprehensive in including so many functions, which truly modernize record keeping and working procedures, and accompany a research scientist into the new century.

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Abstract

The present invention provides an electronic laboratory notebook system and method, for planning a research experiment and recording experimental data in a database. Experimental data, protocol and results, may be retrieved and analyzed using the invention. In one embodiment, the electronic notebook of the invention outputs a pictorial image of experimental samples included in a predetermined experiment. The image may include the concentration of all reagents in a sample, and the location of each sample in the experimental design. In some embodiments, the invention provides budget planning and inventory management, wherein dataflow occurs between various fields allowing automatic depletion of inventory upon performance of an experiment, and allowing preparation of cost estimates for performing an experiment.

Description

COMPREHENSIVE ELECTRONIC LABORATORY NOTEBOOK FIELD OF THE INVENTION
The invention generally relates to the field of Laboratory Information Management Systems (LIMS). More specifically, the invention relates to computer-implemented electronic laboratory notebooks (ELNs), for recording, retrieving and analyzing scientific experimental data.
BACKGROUND
Research scientists working in biotechnology, chemistry, physics, nanotechnology, and environmental research still handwrite their experimental data in a notebook. Typically, a scientist planning an experiment will put a great deal of thought into the hypothesis he wishes to prove or to the goal he wishes to achieve. He will consider which laboratory techniques to take advantage of. For instance, in a biotechnology experiment, he will consider, which cells to culture, which probes to use, and which controls to include in the experiment. He may plan a schedule to determine the time frame of the experiment, and may ascertain that all necessary reagents are at his disposal.
However, when the scientist actually sets down a record of the experiment, he will quickly jot down the intended arrangement of test-tubes in a notebook, and will perform any calculations on a scrap of paper which he will not keep. This leads to human error in, for instance, serial dilutions of reagents, which may easily result in failed experiments. Such an error will go undetected and unexplained, since no record is kept of the dilution calculations, and no quality control exists for the calculations prior to their performance.
Over time, a scientist may not be able to read his own handwriting, or may become uncertain whether the samples were indeed loaded according to the single line of description written in his notebook. As bench work in a laboratory is messy, a physical notebook may become stained or water-logged, with loss of irreplaceable data, which was painstakingly gathered over a period of weeks or months.
Proper documentation is vital to research scientists. A laboratory notebook aims to permanently record what was done on a project and acts as proof of experiments performed. The laboratory notebook has to provide a complete record of activities in a way that allows co-workers to repeat experiments and obtain the same results without having support from the original author. The records in the laboratory notebook should include the object of the investigation, the experimental or theoretical background, a description of the experiment and its parameters, and the experimental results. The need exists for a computerized tool which aids research scientists in planning, recording and analyzing their experiments. The tool should prevent human error which stems from miscalculations in the planning stage. The tool should allow a scientist to easily group and retrieve any experiments having a common denominator, which allows instant recall and comparison of similar topics which he has previously studied, even over a period of years. Often, a scientist will upgrade his personal computer, and not retain hard copies of graphs or experimental data which he feels is unimportant, only to regret this years later when he wishes to return to study the topic once again. The need exists for a tool for data recordation tailored to the needs of a research scientist. Several attempts have recently been made to develop electronic laboratory notebooks (ELNs), to replace paper notebooks in scientific laboratories. For instance, U.S. Pat. Publication 2004/0015514 to Melton et al., U.S. Pat. No. 6,725,232 to Bradley et al., and U.S. Pat. Publication 2007/0208800 to Frohlich et al., all describe databases which allow recordation of experiments tagged with metadata which represents keywords for quick retrieval of similar experiments. Certain additional features are described in these publications, for instance the Frohlich publication provides the ability to time-stamp and digitally authenticate the laboratory records, as is necessary according to FDA regulations. The Bradley patent describes email communication of experimental results, and interaction with users at various remote locations. The Melton publication suggests experimental results may be saved upon a remote server ("cloud computing") to allow access via Internet from any location. U.S. Pat. No. 7,216,113 to Goldwasser. additional describes a method for remotely instructing performance of a scientific experiment, allowing a scientist to order a laboratory procedure from a supplier, such as in the field of chemistry. Experiments can be designed from remote locations, and protocols and inventory can be checked to see if they are suitable and available. Results can be viewed by interfacing with instruments.
However, none of these patent publications provides a tool which includes sufficient functions necessary for running an active research laboratory. The need exists for a complete management system from A to Z in laboratory processes. Such a system should allow design of experiments, computational aid in experimental design, recordation of results, analysis of data, retrieval of linked experiments, budget management, sharing of information between scientists at remote locations, inventory management and search engine capabilities for researching background information necessary for planning an experiment. The present invention provides a comprehensive computerized Electronic Laboratory Notebook (ELN) tool with Laboratory Information Management System (LIMS) features. The ELN of the invention is tailored to the needs of a variety of research fields that may change frequently for a research scientist. This and other objects will become more apparent in view of the Detailed Description of the invention that follows.
SUMMARY OF THE INVENTION In the present invention, the term "data object", used in relation to laboratory research data objects, refers to any details of experiments planned or performed. These include, but are not limited to, the details of reagents, samples, concentrations, protocols, results, bioinformatic results, genetic or protein sequences. The term "data object" as used in the invention additionally includes budget details, inventory lists, user specifics, schedules for performance of tasks .
An electronic laboratory notebook system comprising: computer associated peripherals; a processor configured to interact with the peripherals, by: a)storing a plurality of data objects pertaining to laboratory experiments, in at least one database, the storing performed using data object placement logic, and the data objects are associated with metadata tags; and b) retrieving data objects using metadata logic for retrieval.
In some embodiments, the processor is configured to output a pictorial image of experimental samples of a predetermined experiment, wherein the experimental samples are stored as data objects in the database, hi such case, in some embodiments the outputted pictorial image of experimental samples includes the concentration of reagents in the sample, and includes the location of the sample within a plurality of samples.
Moreover, optionally the database is selected from at least one of the following types: a relational database, a key/value database, and a modified relational database. Further, in some embodiments the data objects in the database are related hierarchically, wherein the first level of hierarchy is an experiments table, the second level of hierarchy is an experimental design table including a list of experimental samples, the third level of hierarchy is a quantity and concentration table, the forth level of hierarchy is a protocol table, and the fifth level of hierarchy is a results table. Additionally, the database may comprise a table of inventory of consumable materials. In such case, data flow may occur between data objects in the inventory table and between associated objects stored in the database in an experimental design table. Further, the database optionally comprises a budget planning table. Optionally, data flow occurs between data objects in the budget planning table, and between associated objects stored in the database in an experimental design table.
Moreover, in some embodiments, the processor is configured to perform one or more of the following functions: output a pictorial image of dilutions included in an experiment, and to calculate reagent concentrations.
Optionally, the processor is configured to perform one or more of the following functions: calculate the cost of an experiment, compute and display a budget remaining, display an alternative reagent, and deplete reagents from inventory using data flow between an experimental design table and between an inventory table.
Additionally, the processor may be configured to perform one or more of the following functions: perform a search of scientific literature using the Internet, send genetic or protein sequences to an external database, upload results from an analytical instrument, and provide a hyperlink for accessing a website providing a bioinformatic tool, store and retrieve data related to experimental research data, retrieve protocols for performance of experiments, display experimental results graphically, perform statistical analysis of experimental results, display inventory, share digital files with another second user at a remote location, schedule tasks to be performed using an analytical instrument, add an authentication to experimental data. In certain embodiments, the system utilizes a server in communication with a remote processing device of a user, wherein the server is configured to perform steps a)-b) and to communicate with the remote processor of the user, using a graphical user interface.
Moreover, the processor may be configured to automatically suggest inclusion of controls deemed to be standard controls in a specific experimental design. Additionally, the processor may be configured to identify experimental results deemed to be abnormal in comparison to previously obtained experimental results.
Further, the processor may be configured to import experimental results from the controlling processor of an analytical instrument.
Still further, optionally, editing of the protocol table results in display of the edited protocol in a marked up fashion illustrating changes made to the protocol.
The invention additionally provides a computer-implemented method for planning a research experiment and recording experimental data, the method comprising the following steps: a) storing an experimental design including details of experimental samples, in a computer readable database; b) storing an experimental protocol associated with the experimental design; c) storing experimental results; d) allowing performance of statistical calculations of the experimental results.
In certain cases, the method may further comprise the step of outputting a pictorial image of the experimental samples.
Additionally, the method further comprises the step of outputting a pictorial image of dilutions to be performed. Further, the method may further comprise the step of storing an inventory table in the database, wherein data flow occurs between objects included in the inventory table and between consumable materials listed in the protocol, and between the experimental samples, such that when an experiment is deemed to have occurred, the inventory table will automatically be depleted respectively. Optionally, the method comprises the step of detecting whether consumable materials included in the experimental protocol are present in an inventory table stored in the database, and alerting a user when the level of the consumable material falls below a predetermined level.
Additionally, the method further comprises the step of entering a budget into the database, wherein data flow occurs between data objects in the budget, and between associated objects stored in an experimental design stored in the database.
The method may additionally comprise the step of scheduling a task on an analytical instrument necessary for the experimental protocol.
The method may further comprise one or more of the following steps: retrieving data related to experimental research data, retrieving a protocol for performance of an experiment, displaying experimental results graphically, performing statistical analysis of experimental results, displaying inventory, sharing digital files with another second user at a remote location, scheduling tasks to be performed using an analytical instrument, adding an authentication to experimental data, performing a search of scientific literature using the Internet, sending genetic or protein sequences to an external database, sending experimental data to a remote user, uploading analytical data from an analytical instrument, and accessing an external website providing bioinformatics analysis tools. In one embodiment, the method utilizes a server in communication with a remote processing device of a user, wherein the server is configured to perform steps a)-d) of the method, and to communicate with the remote processor of the user, using a graphical user interface. The invention additionally provides computer readable storage medium comprising software capable of performing the method of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
For a better understanding of the invention, with regard to the embodiments described, reference is made to the accompanying drawings, in which: Fig. 1 illustrates central tabs provided by the user interface of the invention, including Home, Protocols, Experiments, Analysis, Templates, Inventory, Users and Google Docs.
Fig. 2 illustrates an Experimental Design interactive screen for planning an experiment.
Fig. 3 illustrates a pictorial image of a dilution to perform during an experiment, including reagent volumes and reagent concentrations. The image was outputted automatically after entering some of the dilution parameters.
Fig. 4 illustrates reagents included in an experiment in table form, and illustrates controls which may be added using an Add Control button.
Fig. 5 illustrates an experimental protocol screen.
Fig. 6 illustrates the volumes and concentrations of certain reagents included in an experiment, charted in table form.
Fig. 7 illustrates an inventory screen.
Fig. 8 illustrates a results screen, with results included in spreadsheet format.
Fig. 9 illustrates an experiments screen for retrieval of specific planned or executed experiments. Fig. 1OA illustrates an additional screen for retrieval of specific planned or executed experiments, in which metadata keywords and filter level may be entered.
Fig. 1OB illustrates experiments retrieved during a search, shown in a list format and in a spreadsheet format for comparison of experimental results.
Fig. 11 illustrates a screen for handling genetic and protein sequences. Figs. 12 and 13 illustrate template screens for design of a microwell plate.
Fig. 14 illustrate GoogleDocs™ functions for sharing files between users, for electronic chatting, and for performing statistical and comparative analysis of results.
Fig. 15 illustrates a cell count experiment charted using a data spreadsheet from a GoogleDocs™ tool.
Fig. 16 illustrates a budget planning screen.
Fig. 17 illustrates a task scheduling screen.
Fig. 18 illustrates a screen listing users with permission to access the system.
Figs. 19-22 describe screens allowing a user to performing a calculation relevant to several samples included in an experiment.
Fig. 23 is a flow chart illustrating the data flow and hierarchy of the modules that form the invention.
Fig. 24 is a diagram illustrating implementing the invention using a remote server, in a cloud computing environment. It will be appreciated that for simplicity and clarity of illustration, elements shown in the drawings have not necessarily been drawn accurately or to scale. Reference numerals may be repeated among the drawings to indicate corresponding or analogous elements. Moreover, some of the blocks depicted in the drawings may be combined into a single function.
DETAILED DESCRIPTION OF THE INVENTION
In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. There is no intention to limit the invention to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.
In the following detailed description the invention is described in relation to functions and experiments typical for a research scientist in the field of molecular biology. This is for illustrative purposes only, and the invention may be utilized with experimental data originating in any field of interest. The scope of the invention is not limited to use with life sciences alone, rather includes for instance, physics, nanotechnology, chemistry, ecology, environmental research, and numerous other fields.
The present invention provides a comprehensive Electronic Laboratory Notebook (ELN) which simplifies all aspects of running an active laboratory, from planning to execution of an experiment, and provides computational analysis of results, inventory management, budget planning, scheduling of tasks or instruments, sharing of experimental data between scientists at remote locations, posting new sequences to online biological databases, and performance of a scientific literature search.
The invention additionally can be used to perform a bioinformatics search, which may include, for instance, use of software for statistical comparison of genetic or protein sequences, or access of genetic/protein databases such as GenBank or BLAST (both of the NCBI, belonging to National Institutes of Health (NIH), Bethesda MD). The invention may be used to obtain access to additional bioinformatics tools and advanced statistical tools. The invention may be used to order materials, devices or products from appropriate vendors using the internet. The ELN of the invention conforms to regulatory procedures by allowing digital signatures and time stamps to be added to documents.
Additionally, the invention can instantaneously provide a pictorial version of the experimental samples and automatically calculate dilutions and concentrations, thus preventing miscalculations during experimental design, which can doom an entire week- long experiment. Automatic generation of such a visual aid has not been previously described in the art. Similarly, automatic calculation of dilutions and final concentrations is not known in the art.
Relevant scientific literature may be searched, and the search results may optionally be saved to the system's memory in association with a specific experiment. Search results may include literature documents, links, bioinformatics results, and references to prior experiments or prior results. Search results may include searching information obtained, keywords used, and their context or relation in the search (e.g. search at experiments, protocols, by users, etc.). The ELN of the invention provides access to bioinformatics tools, chemoinformatics tools, statistical tools and allows searches of external database (e.g. for primer design, BLAST, for searching genome/protein databases, to design molecules, etc.).
All functions are provided instantly, at the touch of a button. Such an all encompassing electronic laboratory notebook has not been previously described in the art, and is invaluable for a modern research scientist. Referring now to Figure 1, the graphical user interface (GUI) of the invention is a tabbed document interface (TDI), which allows navigation between windows by selecting a tab using the mouse (or using another computer-associated peripheral). For instance, in Fig. 1, the tabs shown include a "Home" tab 100, a "Protocols" tab 200, an "Experiments" tab 300, an "Analysis" tab 400, a "Templates" tab 500, an "Inventory" tab 600, a "Users" tab 700 and a "Google Docs®" tab 800. Each of these central tabs will be discussed in detail herein-below.
Upon opening the software of the invention, the initial screen depicted in Fig. 1 illustrates a list of the active tasks 10, active experiments 12 and active projects 14 entered by the scientist. A user may return to this initial screen by selecting the Home tab 100.
Selection of a specific active experiment 12, such as the "MG cond2" experiment 16, by clicking on the "edit" icon 18 related to this experiment, will open a new screen, illustrated in Fig. 2. Alternatively, a user may choose to open a new experiment, which he may title as desired, and may continue to the screen described in relation to Fig. 2.
Referring to Fig. 2, at left, clicking upon Introduction 20 will allow editing of the Introduction related to a specific experiment. A new editable window will open, allowing the scientist to type in any desired text, such as a description of the background, aim of the experiment, etc. Graphical data, video or bioinformatics results may be added as well, as a visual aid, and all text will be saved and associated with the new experiment, which the scientist titles as he wishes.
Keywords, also termed "metadata", describing the important aspects of the experiment may be added, and will aid in retrieval of experiments linked with a common denominator such as a common topic, common experimental technique, a specific individual performing the research, etc. Non-limiting examples of metadata which may aid in subsequent retrieval of specific experiments include: the title, subject, description, source, language, relation, coverage, name of user, date, type, format and identifier.
The scientist may then choose to plan the experiment, by clicking on Experimental Design 22. A new screen will be presented, illustrated in Fig. 2
Referring to Fig. 2, a user may click on buttons Add Reaction 24, Add Tube 26, or Add Plate 28. These allow recordation of new reactions, of additional related test-tubes, or of a new microwell plate. Reagents which were previously entered by the user appear in table style, under the headings: Reagent 30, Quantity 32 and Final Concentration 34. Each reagent entered may be edited, or removed, by clicking on Change 36 or on Remove 38. New reagents may be added by clicking on Add Reagent 40 (bottom of Fig. 2). The invention aids in performing mathematical calculations necessary for performance of most experiments, such as serial dilutions of reagents or reactants. A visual image of the test-tubes and how to perform the dilution is presented to the user at the click of a button.
For instance, referring to the chart in Fig. 2, the first charted line 40 requires performance of 4 serial dilutions of Mg 100 mM. Clicking on Change 36 adjacent to the first line, opens a new window, shown in Fig. 3, which details the dilution and pictorially shows how to perform the dilution.
Referring to Fig. 3, once the parameters of the dilution are entered (e.g. the quantity of the material 42, the highest concentration 44, the dilution factor 46, and the number of dilutions 48), the software immediately calculates the amount of each reagent necessary to reach the proper dilution, and outputs a picture 50 of the microtubes and of the amount of each reagent per tube. Such a pictorial depiction has not been previously available at the touch of a button. This prevents miscalculations and records the dilution process for future viewing. A printout may be taken to the lab-bench, for easy reference during actual performance of the experiment, while records of the Experimental Design and chart of reagents used are retained in the system memory.
Referring to Fig. 4, control microtubes may be added by clicking on Add Control 51 (at the bottom of Fig. 4). Controls are saved to the system's memory in two manners: linked to the specific experiment, and saved by searchable keywords, for automatic retrieval when a new experiment is designed using a similar protocol. Thus, for instance, since the specific PCR experiment shown in Fig 4, includes a Negative Control 52 (without the DNA template), and a positive control 54, the system will cue the user in a future PCR experiment and will ask whether to include these or similar controls.
Referring to Fig. 5, in order to add the protocol describing specific instructions for performance of the experiment, the user may click on Procedure 56, to open the screen shown in Fig. 5. The user may either type in the protocol, as shown in Steps 1-8 of Fig. 5, or may import it from another location by clicking on Add Document 58. Alternatively, the user may select the tab Protocols 200 (from the main menu), to access protocols stored in the system's memory. Protocols may include widely published laboratory technique protocols, such as molecular biology techniques published by Maniatis, et al., "Molecular Cloning; A Laboratory Manual" (Cold Spring Harbor Lab, New York, 1982. Alternatively, protocols may be those specifically developed or fine-tuned by the user or his colleagues.
Should the user wish to edit a widely accepted protocol, he may select the Edit tab 59, and may type in the changes, which will appear in Marked Up format (showing additions in underline), in conformity to FDA regulations. A user may select the Sign tab 61, to add a digital authentication, date/time stamp, and seal the record from further editing.
Such authentication adds legalization to the documents saved, and is required by regulatory bodies (such as the FDA). The ELN complies with the Good Laboratory
Practice (GLP) standard, and includes data history, etc., in compliance with 21 CFR Part 11, FDA.
Referring to Fig. 6, samples 1-4 are charted in Table form, detailing the experiment itself, including a list of all reagents to be added, and including the concentration and quantity of each reagent. Samples are numbered.
Data flow exist between various screens, so that for instance, when the user informs the system that the experiment has been performed, the software of the invention will automatically update the list of Inventory 600, indicating depletion of quantities of consumable reagents which were used in the experiment.
Referring to Fig. 7, the Inventory 600 tab is illustrated. Materials which were consumed in the experiment performed (best shown in Fig 2), will automatically be depleted from the Inventory, relative to the amount consumed. For instance, in this case, forward primer 60, PCR buffer 62, reverse primer 64, Taq DNA polymerase 66 are some of the materials used in the experiment shown in Fig. 2, and the amount consumed will be adjusted in the Inventory. Appropriate flags will appear onscreen to indicate to the user that a specific material is in danger of depletion and should be reordered. The supplier information is available from the Supplier menu 68, and materials may be ordered online using a link to relevant suppliers. Should the user wish to view similar materials, such as when planning an experiment, or when a material is indeed in danger of immediate depletion and the user would like to search for a substitute, the Material Type menu 70 lists materials by type (e.g. antibiotics, buffers, DNA templates, primers, culture mediums), and allows performance of an internal database search to detect materials of a similar nature.
Referring back to Fig. 6, results may be viewed by clicking on Results 72 (left bottom). This will open a new screen, described in relation to Fig. 8.
Referring to Fig. 8, results 72 may be charted by typing them in manually into the spreadsheet 74. Analysis of results, including all typical spreadsheet computations may be made by selecting any of the dropdown menus 76 or buttons 80 of the spreadsheet, or by using widely known spreadsheet commands or shortcuts. The results may be presented in graph format.
In another embodiment, results may be saved as Microsoft Office documents (Word, Excel), as photos, drawings, etc. Alternatively, results may be imported directly from the instrument in which the experiment was performed by selecting the Add Document tab 82 (top left). The software of the invention can interface with certain predetermined laboratory instruments which have controlling processors, to obtain the results of an experiment such as an experiment recently run. Results are uploaded to the properly linked database location. Virtually all modern analytical devices and instruments are operated by a controlling computer and accordingly experimental results are provided in electronic form. Though a research laboratory typically has many different such devices, which may originate in various manufactures, the ELN of the invention advantageously can seamlessly integrate the experimental data and results produced by some of these analytical devices and instruments, by means of an instrument interfacing module. Non-limiting examples of instruments which one may envision interfacing with, include: an ELISA microplate reader, a PCR thermocycler, an HPLC system, a mass spectrometer, infrared thermography instruments, chromatography instruments, capillary electrophoresis instruments, optical reflection instruments, optical transmission instruments, viscometry instruments, mechanical resonators, solubility instruments, differential scanning calorimetry instruments, elongation instruments, indentation instruments, deformation or spectroscopy instruments.
Referring now to Fig. 9, the Experiments tab 300 has been selected, to search for and retrieve specific experiments that have been performed or are planned. Searching may be performed by entering metadata keywords in the Search For 84 field. Searching may optionally be according to the Date 86.
Referring to Fig. 1OA, the Analysis tab 400 has been selected, to open the screen illustrated. After using the dropdown menus Form 88, Project 90, to specify which experimental data to retrieve, the user may select three fields 91 of metadata keywords to search through in order to retrieve one or several experiments saved in the database of the system. The filter condition 93 may be selected as well, in order to fine-tune the search. After pressing the Get Data button 95, any relevant experiments will be retrieved from the database of the invention. Search results are shown in Fig. 1OB. Referring to Fig. 1OB, the search results obtained are illustrated in table format 97, which indicates the experiment title 99 and the relevancy levels 101 of the fields searched. A user may press on the Create Spreadsheet button 103, to plot the experimental results from several experiments in a comparative spreadsheet 105, which may optionally be viewed as a plotted graph. This allows analysis of experiments having related subject- matter. For instance, one may view how changing a specific parameter affected the results obtained, such as changing the cell source used, or changing the enzymes or reaction conditions. One may view changes in results obtained in various timeframes (e.g. mature test animal vs. immature test animal).
Referring back to Fig. 1OA, clicking on Sequences 94 will open a new window for handling genetic and protein sequences, shown in Fig. 11. Referring to Fig. 11, genetic and protein sequences may be searched and viewed. Search may be based on the Accession 96 number issued to the sequence. The search may be performed either in the internal database of the invention, or in external genetic databases open to the public, such as Genbank (of the NCBI, belonging to National Institutes of Health (NIH), Bethesda MD). A new sequence file may be submitted to Genbank using the Upload Genbank File field 98.
Referring to Fig. 12, Templates tab 500 has been selected, to open the screen shown for design of an experiment performed on a microwell plate. The software identified two templates of microwell plates which can be used to design a new experiment, as shown in the list titled "2 Plate Templates Found" 102. Alternatively, the user may select any of the buttons "New 6 well plate" 104, "New 24 well plate" 106, etc. Selection of "New 24 well plate" 106 opens the window shown in Fig. 13.
Referring to Fig. 13, a 24-well plate is illustrated in pictorial form 108, which can be printed out for use at the lab bench during performance of the experiment. User first enters sample groups 110 (T1-T3), and selects whether samples should be placed horizontally or vertically in the microwells. The sample groups 110 are color-coded upon the pictorial form 108 of the microwell plate, for visual clarity during performance of the experiment. A key for the color coding is provided adjacent to the picture image of the microwell plate, detailing which color is associated with which sample group.
Referring to Fig. 14, the GoogleDocs™ tab 800 has been selected to allow a user to collaborate with research scientists at remote locations by sharing any files of interest using the Share button 112. Clicking on the More Actions button 113 opens a chat option, so that a user may initiate an online dialog with a researcher at a remote location, to discuss for instance, a data chart they are both viewing simultaneously using the Share 112 option. Clicking on the Search Templates button 114 allows access of tools provided by Google™, such as Correlative Statistics, for additional data analysis opportunities. Clicking on Show Search Options 115 will allow a user to perform an external search of scientific literature using the Internet, to reach for instance, PubMed or any other journal articles published online. Additional search options which may be selected from using this menu, include BLAST (of the NCBI, belonging to National Institutes of Health (NIH), Bethesda MD), which provides searching and statistical evaluation of matches within genome/protein databases. BLAST software additionally is available to design molecules, or primers. In some embodiments, the Search Options menu provides a hyperlink for accessing these or other bioinformatics tools.
Referring to Fig. 15, a cell count experiment has been charted by opening a data spreadsheet using a GoogleDocs™ tool. The chart may be edited, or may be sent to additional users.
Referring to Fig. 16, the Home tab 100 has been selected, followed by Projects 116, to reach a budget-planning option. Individual projects may be scheduled, and their budget entered in the fields Budget 118, and Current Budget 120. When the user indicates that the experiment has been performed, the budget remaining will be adjusted accordingly. Optionally, the prices of consumable reagents used, can be automatically obtained from the Inventory database by data flow, so that upon planning of the experiment the user will be made aware of the cost of the experiment planned.
Referring to Fig. 17, task scheduling is available by clicking on Tasks 122 after selecting the Home tab 100. Dates may be entered in Start Date 124 or Due Date 126 fields, individual Assigned Users 128 may be entered, and after pressing the Save Task button 130, a screen will open to allow a user to schedule use of specific instruments, which are typically shared by multiple users.
Referring to Fig. 18, Users tab 700 opens a screen listing which users are currently logged on. Selecting a specific user from the list will open a new screen indicating which files they have permission to access. Pressing the New User button 132 allows addition of new users.
Figs. 19 through Fig. 22 describe the instance in which a planned experiment entails performing a calculation which is relevant to several samples and the user wishes to establish a linkage between the calculation and between specific samples.
Referring to Fig. 19, the Add Form button 134 may be pressed to open a new screen
(described in relation to Fig. 20) in which the calculation may be set up and linked to the appropriate samples.
Referring to Fig. 20, the user wishes to generate a form, in which the optical density
(OD) obtained in a first measurement is summed with the OD obtained in a second measurement. The user may select the fields to relate as being "ODl" 136 and "OD2" 138, and then select the term formula 140 from the drop-down menu. After pressing the OK button 142, the next screen shown in Fig. 21 will open.
Referring to Fig. 21, the field Sum 144 has been entered, and the field type Formula 146 and Return the Sum of all Numbers 148 have been selected from the wide variety of calculation options available in drop-down menu 150. Clicking on the Save Form button 152 will save this calculation.
Referring to Fig. 22, the samples Alb through A6b 154 listed in the table 156 have been associated with the sum calculation established in relation to Figs. 20, 21, so that the sums of ODl and OD2 will appear at the right of each sample, under the heading Sum 158. Additional samples may be entered in the field Associate with Reaction Tubes 160, to allow this sum to be calculated for any other samples of interest.
This form will automatically become associated with the protocol used to perform this experiment, so that a user planning a similar experiment will be queried whether to include this calculation in the new experiment.
The ELN software of the invention is operable from any suitable computer, computer system or related group of computer systems known in the art. In one embodiment, the software is installed upon a server or server computer system which is connected by at least one input/output port to a communication network. The communication network may be a local area network connecting a plurality of computers via any suitable networking protocol, including but not limited to Ethernet. In another embodiment, the communication network is the Internet and the system comprises server software capable of communicating with client computers via the Internet via any suitable protocol, including but not limited to HTTPS. In such case, the invention may be provided to a user as software as a service (SaaS) which will obviate a user from hardware needs such as a server and necessary server maintenance, security, etc. In one embodiment, a user may use a browser such as Internet Explorer™, Mozilla Firefox, Chrome or Safari, to browse on the server via the internet. Any processing device may be utilized, including for instance, a personal computer, a laptop, a PDA or a cellular phone. The invention is embodied in any suitable programming language or combination of programming languages, including Google Web Toolkit, JAVA, database managers and MySQL.
Each software component can be implemented in a high-level procedural or object- oriented programming language, or in assembly or machine language if desired. The programming language may be a compiled or interpreted language.
Specific experiments planned or performed by a user are entered into and saved in a database which may be any suitable database for storing data objects and metadata relating thereto. Any suitable database program may be used. In one embodiment, the database is a relational database and a key/value database. In one embodiment, database is a modified relational database. The search logic used for subsequent retrieval of experiments from the database, is any suitable step, process, function or series of steps, processes and functions known in the art for searching a database. Each workstation includes a graphical user interface (GUI). The contents of the screens, the functionality of the system and the work process may be adjustable to a user's needs. The screen designs, terms and work process reflect the scientific field and are user- friendly since they display and interact with the user in syntax familiar to a life sciences research scientist. Thus use of the system appears intuitive. The objects (interactive fields) in the ELN are updated in real time. In some embodiments, there is complete data flow between certain of the objects. In some embodiments, the objects are modular. Thus, the user can work with few or all of the objects of the invention according to his needs at a given time. The modularity allows integration with a variety of tools accessible on the Internet, using links provided by the invention.
The invention can be implemented using digital electronic circuitry, or in computer hardware, firmware, software, or in combinations of them.
Referring to Fig. 23, a flow chart is shown, illustrating the data flow and hierarchy of the modules that form the invention. Data may flow in both directions from modules depicted on the periphery of the flow chart (inventory, devices, samples, collaborators, project management, task management), towards, or out from, modules depicted at the center of the flowchart. Inner modules represent central screens of the invention, pertaining to specific experiments planned or performed (introduction, experimental design, procedures, experiment comparison analysis, etc.). Referring to Fig. 24, in some embodiments the invention is implemented in cloud computing using a remote server. Cloud computing refers to using a personal computer or PDA to to access a server running the software of the invention, via the internet. The graphical interface of the application appears the same for all users and organizations, and uses the same database upon the server, however each user is identified according to the organization he is affiliated with, and can view only his secured data. Users can choose to share data with external users to the organization or to work in a collaborative space set aside for all users and organizations.
Suitable processors for implementation of the invention include, by way of example, both general and special purpose microprocessors. Generally, a processor will receive instructions and data from a read-only memory and/or a random access memory.
Generally, a computer will include one or more mass storage devices for storing data files; such devices include magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and optical disks. Storage devices suitable for tangibly embodying computer program instructions and data include all forms of non-volatile memory, including by way of example semiconductor memory devices, such as EPROM, EPROM, and flash memory devices; magnetic disks such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM disks.
The electronic lab notebook of the invention accommodates all aspects of conducting a laboratory, including planning and executing experiments, and recording and analysis of results. The invention further allows on-demand bio-informatics, on-demand calculators, on-demand analysis, full integration of statistical tools, real time ERP (Enterprise Resource Planning), real time business intelligence (BI) and real time executive managers dashboard for summaries and control the organization and particular the lab resource.
The software of the invention can learn. It is capable of identifying extreme deviations in the experimental results, and thus identifying and isolating potentially false results. It is dynamic in its ability to cope with user error during an experiment or to identify repeated failures such as extreme deviations obtained by different users, for example, as a result of a damaged component. Thus, the system reduces inaccuracies resulting from human errors. In summary, the Electronic Laboratory Notebook (ELN) of the invention provides an extremely comprehensive tool for running an active research laboratory. In addition to record keeping and quick data retrieval, the invention provides previously unknown tools such as a pictorial image of samples and of dilutions to perform. This image may be printed out and taken to the lab bench during performance of the experiment. Another novel tool is automatic calculation of reagent concentrations, which prevents error in experimental design, thus vastly increasing repeatability of experiments.
Significantly, certain data fields are related and allow data flow between fields, so that inventory is automatically depleted when the experiment is deemed to have been performed. Similarly, the overall cost of a specific experiment may be readily determined based on the consumable reagents included in the experimental design, and the remaining budget can be adjusted accordingly. This allows a researcher to predict in advance whether the cost of the experiment makes its execution feasible. As reagents are grouped in the inventory database according to common denominators, costly reagents may be replaced with less expensive reagents prior to performance of the experiment.
The invention allows protocols to be retrieved at the touch of a button, allows computation and analysis of results, and allows sharing of experimental data between remote locations, which promotes scientific collaboration. When the software of the invention is saved upon a server accessible using the Internet, all data may be accessed from any location, allowing a visiting scientist access to data from his home laboratory.
The ELN of the invention is comprehensive in including so many functions, which truly modernize record keeping and working procedures, and accompany a research scientist into the new century.
It should be apparent that many modifications, substitutions, changes, and equivalents might occur to those of ordinary skill in the art.
Having described the invention with regard to certain specific embodiments thereof, it is to be understood that the description is not meant as a limitation, as further modifications will now become apparent to those skilled in the art, and it is intended to cover such modifications as are within the scope of the appended claims.

Claims

1. An electronic laboratory notebook system comprising: i) computer associated peripherals; ii) a processor configured to interact with said peripherals, by: a) storing a plurality of data objects pertaining to laboratory experiments, in at least one database, said storing performed using data object placement logic, and said data objects are associated with metadata tags; and b) retrieving data objects using metadata logic for retrieval.
2. The electronic laboratory notebook system of claim 1, wherein said processor is configured to output a pictorial image of experimental samples of a predetermined experiment, wherein said experimental samples are stored as data objects in said database.
3. The electronic laboratory notebook system of claim 2, wherein said outputted pictorial image of experimental samples includes the concentration of reagents in said sample, and includes the location of said sample within a plurality of samples.
4. The electronic laboratory notebook system of claim 1, wherein said database is selected from at least one of the following types: a relational database, a key/value database, and a modified relational database.
5. The electronic laboratory notebook system of claim 1, wherein said data objects in said database are related hierarchically, wherein said first level of hierarchy is an experiments table, the second level of hierarchy is an experimental design table including a table of experimental samples, the third level of hierarchy is a quantity and concentration table, the forth level of hierarchy is a protocol table, and the fifth level of hierarchy is a results table.
6. The electronic laboratory notebook system of claim 1, wherein said database comprises a table of inventory of consumable materials.
7. The electronic laboratory notebook system of claim 6, wherein data flow occurs between data objects in said inventory table and between associated objects stored in said database in an experimental design table.
8. The electronic laboratory notebook system of claim 1, wherein said database comprises a budget planning table.
. The electronic laboratory notebook system of claim 8, wherein data flow occurs between data objects in said budget planning table, and between associated objects stored in said database in an experimental design table.
10. The electronic laboratory notebook system of claim 1, wherein said processor is configured to perform one or more of the following functions: output a pictorial image of dilutions included in an experiment, and to calculate reagent concentrations.
11. The electronic laboratory notebook system of claim 1, wherein said processor is configured to perform one or more of the following functions: calculate the cost of an experiment, compute and display a budget remaining, display an alternative reagent, and deplete reagents from inventory using data flow between an experimental design table and between an inventory table.
12. The electronic laboratory notebook system of claim 1, wherein said processor is configured to perform one or more of the following functions: perform a search of scientific literature using the Internet, send genetic or protein sequences to an external database, upload results from an analytical instrument, and provide a hyperlink for accessing a website providing a bioinformatic tool.
13. The electronic laboratory notebook system of claim 1, wherein said processor is configured to perform one or more of the following functions: store and retrieve data related to experimental research data, retrieve protocols for performance of experiments, display experimental results graphically, perform statistical analysis of experimental results, perform calculations related to predetermined samples included in an experiment, display inventory, share digital files with another second user at a remote location, schedule tasks to be performed using an analytical instrument, add an authentication to experimental data.
14. The electronic laboratory notebook system of claim 1, wherein said system utilizes a server in communication with a remote processing device of a user, wherein said server is configured to perform steps a)-b) of storing and retrieving data objects, and to communicate with said remote processor of said user, using a graphical user interface.
15. The electronic laboratory notebook system of claim 5, wherein said processor is configured to automatically suggest inclusion of controls deemed to be standard controls in a specific experimental design.
16. The electronic laboratory notebook system of claim 5, wherein said processor is configured to identify experimental results deemed to be abnormal in comparison to previously obtained experimental results.
17. The electronic laboratory notebook system of claim 5, wherein said processor is configured to import experimental results from the controlling processor of an analytical instrument.
18. The electronic laboratory notebook system of claim 5, wherein editing of said protocol table results in display of said edited protocol in a marked up fashion illustrating changes made to said protocol.
19. A computer-implemented method for planning a research experiment and recording experimental data, said method comprising the following steps: a) storing an experimental design including details of experimental samples, in a computer readable database; b) storing an experimental protocol associated with said experimental design; c) storing experimental results; d) allowing performance of statistical calculations of said experimental results.
20. The method of claim 19, further comprising the step of outputting a pictorial image of said experimental samples.
21. The method of claim 19, further comprising the step of outputting a pictorial image of dilutions to be performed.
22. The method of claim 19, further comprising the step of storing an inventory table in said database, wherein data flow occurs between objects included in said inventory table and between consumable materials listed in said protocol, and between said experimental samples, such that when an experiment is deemed to have occurred, said inventory table will automatically be depleted respectively.
23. The method of claim 19, further comprising the step of detecting whether consumable materials included in said experimental protocol are present in an inventory table stored in said database, and alerting a user when the level of said consumable material falls below a predetermined level.
24. The method of claim 19, further comprising the step of entering a budget into said database, wherein data flow occurs between data objects in said budget, and between associated objects stored in an experimental design stored in said database.
25. The method of claim 19, further comprising the step of scheduling a task on an analytical instrument necessary for said experimental protocol.
26. The method of claim 19, further comprising at least one of the following steps: retrieving data related to experimental research data, retrieving a protocol for performance of an experiment, displaying experimental results graphically, performing statistical analysis of experimental results, performing calculations related to predetermined samples included in an experiment, displaying inventory, sharing digital files with another second user at a remote location, scheduling tasks to be performed using an analytical instrument, adding an authentication to experimental data, performing a search of scientific literature using the Internet, sending genetic or protein sequences to an external database, sending experimental data to a remote user, uploading analytical data from an analytical instrument, and accessing an external website providing bioinformatics analysis tools.
27. The method of claim 19, wherein said method utilizes a server in communication with a remote processing device of a user, wherein said server is configured to perform steps a)-d) and to communicate with said remote processor of said user, using a graphical user interface.
28. Computer readable storage medium comprising software capable of performing the method of claim 19.
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