# Difference between revisions of "Journal:Implementation and use of cloud-based electronic lab notebook in a bioprocess engineering teaching laboratory"

Full article title Implementation and use of cloud-based electronic lab notebook in a bioprocess engineering teaching laboratory Journal of Biological Engineering Riley, Erin M.; Hattaway, Holly Z.; Felse, P. Arthur Northwestern University Email: afelse at northwestern dot edu 2017 11 40 10.1186/s13036-017-0083-2 1754-1611 Creative Commons Attribution 4.0 International https://jbioleng.biomedcentral.com/articles/10.1186/s13036-017-0083-2 https://jbioleng.biomedcentral.com/track/pdf/10.1186/s13036-017-0083-2 (PDF)

## Abstract

Background: Electronic laboratory notebooks (ELNs) are better equipped than paper laboratory notebooks (PLNs) to handle present-day life science and engineering experiments that generate large data sets and require high levels of data integrity. But limited training and a lack of workforce with ELN knowledge have restricted the use of ELN in academic and industry research laboratories, which still rely on cumbersome PLNs for record keeping. We used LabArchives, a cloud-based ELN in our bioprocess engineering lab course to train students in electronic record keeping, good documentation practices (GDPs), and data integrity.

Results: Implementation of ELN in the bioprocess engineering lab course, an analysis of user experiences, and our development actions to improve ELN training are presented here. ELN improved pedagogy and learning outcomes of the lab course through streamlined workflow, quick data recording and archiving, and enhanced data sharing and collaboration. It also enabled superior data integrity, simplified information exchange, and allowed real-time and remote monitoring of experiments. Several attributes related to positive user experiences of ELN improved between the two subsequent years in which ELN was offered. Student responses also indicate that ELN is better than PLN for compliance.

Conclusions: We demonstrated that ELN can be successfully implemented in a lab course with significant benefits to pedagogy, GDP training, and data integrity. The methods and processes presented here for ELN implementation can be adapted to many types of laboratory experiments.

Keywords: electronic lab notebook, good documentation practice, data integrity, experiment workflow, pedagogy

## Background

Data recording and reporting is of highest importance in all types of research. Data that is not recorded or recorded incorrectly is summarily invalid. Academic teaching laboratory courses have emphasized the importance of accurate record keeping and extensively trained students in good documentation practices (GDPs) based on paper lab notebooks (PLNs). Though the use of PLNs has been perfected over several decades, the large data sets generated by many contemporary life science experiments are better managed through electronic laboratory notebooks (ELNs). But the academic community has been generally slow in moving towards the use of electronic laboratory notebooks.[1][2] Lack of resources, non-standardized regulations, data security concerns, and low activation energy for changes contribute to poor adoption of ELN in academia.[3] As a result, only about five percent of academic labs use ELNs.[4] Agencies such as the National Institutes of Health (NIH) routinely emphasize the importance of data sharing and reproducibility. A report from the NIH concluded that the main reason for non-reproducibility of research data is the lack of good documentation methods rather than scientific misconduct.[5] ELNs can facilitate data sharing and simplify good documentation practices, and subsequently improve reliability of scientific data better than PLNs.[6] Also, ELNs can simplify recording and archiving of large data sets such as those generated in -omics research and in core laboratories.[7]

In this paper we present the implementation and use of LabArchives, a cloud-based ELN software in our bioprocess engineering laboratory course. The multitude of pedagogical objectives accomplished through the use of LabArchives ELN is summarized in Fig. 1. For students, LabArchives facilitated legible and quick data recording, improved data sharing and collaboration, and streamlined the lab notebook submission process. For instructors, it facilitated real-time monitoring of experiment workflow, ease of grading and feedback, and simplified information sharing with students. For the lab course, it enabled superior data integrity and quality through reliable audit trails and efficient archiving of data. We also present an analysis of students’ responses on the use of the ELN, our development actions to improve student experience, and a proposal of future directions.

 Figure 1: Pedagogical goals accomplished through ELN

### Rationale for using ELN in a teaching laboratory

PLNs have been used by both academia and the industry even since data collection began.[20] PLNs are still widely used, but they cannot accommodate the large sets of data generated by today’s life science experiments.[21] Legibility, data integrity, security, and archiving of PLNs are a huge logistical and financial burden. Inefficiencies inherent in using PLNs costs the drug industry about \$1 billion annually by way of lost data sharing opportunities and redundancy in data generation.[22] ELNs can effectively address several disadvantages associated with PLNs. ELNs facilitate better workflow, quick data retrieval, remote accessibility of data, and enables superior data integrity. A recent article in Science Careers identified knowledge in using ELNs as one of the key tools for successful careers in the science and technology industry.[23] We included ELN training in the bioprocess engineering lab course to better prepare students for careers in the biotechnology industry, to streamline workflow in the teaching lab, to facilitate data sharing and collaboration among student teams, and to create a culture of ELN use for the future workforce.

## Methods

### The bioprocess engineering lab course

The bioprocess engineering lab course is a graduate course offered to students in the Master of Biotechnology program at Northwestern University. The lab course includes hands-on training in bench-scale upstream and downstream bioprocessing methods, good laboratory practice, design of experiments, quality and validation, team skills, and written communication skills. Experiments are done in three- or four-member student teams, and teams perform experiments on a rotating schedule. Students are expected to share data between teams and collaborate in data analysis. All experiments need data collection at multiple time points by different team members which should be recorded using a streamlined process. Experiments in this lab course generate extensive digital data (such as preparative chromatography and bioreactor experiments) which are exported as Excel or CSV files. Students in this lab course primarily have undergraduate degrees in biology, biotechnology, or chemical engineering. Students are distributed in teams based on their educational and cultural backgrounds, gender, and personality type (based on Meyers-Briggs personality type assessment).

### Implementation of ELN in the bioprocess engineering lab course

LabArchives subscriptions were purchased at about the same cost as PLN on a per student basis. Each student created an individual account and therefore we were able to track each entry with username and time stamp. The instructor populated the master ELN with folders and files with information on all experiments. Information included a list of supplies and chemicals needed for the experiment, equipment operating manuals, calibration and preparation procedures, safety information on equipment, and safety data sheet documents. LabArchives was the single point source for information retrieval and data recording. All folder structures and information contained in the folders were then cloned into student notebooks as shown in Fig. 2. LabArchives allows for regular update of information provided by the instructor, so it was possible to communicate new information to students instantly as they became available.

 Figure 2: Screenshot of LabArchives’ document and folder system. All indented titles are contained within the folders above them.

Once students were placed in teams, each team chose a notebook leader in whose electronic notebook the data would be submitted for the entire term. The team notebook leader then shared their notebook and gave the team members the ability to view and edit the notebook as well as to turn in the assignments for grading. The assignments could be submitted by checking the assignment submission button, at which point the notebook is unable to be further edited, and timestamps ensured that the notebooks were submitted on time. The team notebook leader was also able to share their notebook with students in other teams by giving them view-only privileges to certain pages. This guaranteed data integrity while allowing the teams to share their data with others for collaborative learning.

Revisions made to LabArchives entries by students are tracked collectively for the team based on the team’s (notebook leader’s) user identification. But it was required for the student making the revisions to identify themselves and enter the reason for revision in the comments section. Thus all revisions were attributed to a particular student making the revision. Revisions made without identity were considered to be non-compliant and invalid. Attribution at the student level promotes strict compliance from all students, and makes it possible to trace the complete history of changes if necessary.

### ELN user experience evaluation

After the bioprocess engineering lab course offerings in 2015 and 2016, students were asked to complete an exit survey on the use of the ELN for course development proposes. SurveyMonkey was used to deploy the survey questions and collect feedback. The survey included queries related to ELN use, introductory lecture, and compliance, among others. Data related to student experiences in using ELN were extracted from this survey and analyzed. The lab course had enrollments of 38 and 33 students during 2015 and 2016 respectively. Student response counts for the survey were 32 (84.2% response rate) and 23 (70% response rate) during 2015 and 2016 respectively. All students who responded to the survey completed it in entirety.

Survey queries used in this study are shown in Table 1. Student experiences on various attributes important to ELN use were assessed using the Likert Scale (Query 1). Statistical significance of differences in student responses between 2015 and 2016 course offerings were evaluated using a two-sample t-test assuming unequal variances. Time taken for the students to become comfortable with the ELN was quantified as number of weeks (Query 2). Time taken for students to become comfortable with ELN use in a particular year was estimated using a weighted average composite score defined as:

${\displaystyle Compositescore=\Sigma \left(timetakentobecomecomfortable\times \%ofstudentsreportingthistime\right)}$

 1 (poor) 2 (passable) 3 (neutral/adequate) 4 (very good) 5 (excellent) Table 1. Queries used in user experience evaluation survey Query 1: Please rate your experiences in the following attributes in using ELN. Attribute Score (pick one) Introductory lecture Submission Data sharing Accessibility Query 2: How many weeks did it take for you to become comfortable with ELN software (pick one)? 1 2 3 4 5 Still not comfortable Query 3: Which system makes it easier to comply with academic rules and expectations for the lab course (pick one)? Electronic is eastier Paper is eastier Both are same Query 4: Please rate your experiences in completing the following tasks in ELN compared to PLN. Task Score (pick one) Data entry Adding figures Data sharing Editing information

Students reporting “still not comfortable” were assigned six weeks, which is the minimum time it would take for them to become comfortable with the ELN. Student perceptions on ELN vs. PLN for compliance with academic rules and expectations were queried using a multiple choice question (Query 3). Comparison of student experiences in completing documentation and data sharing tasks using ELN vs. PLN was assessed using the Likert Scale (Query 4).

## Results and discussion

### Experiment workflow using LabArchives

The general workflow and use of LabArchives in each step of an experiment is shown in Fig. 3. Each experiment had a set of tasks to be completed by different people before, during, and after the experiment. LabArchives was used to manage these tasks in a streamlined manner. LabArchives also provided a platform for interactive exercises such as protocol revision.

 Figure 3: General workflow of the lab experiment showing the role of ELN. Tasks that were done through LabArchives are shown in boxes with broken lines.

### Protocol writing

Student teams were assigned experimental goals ahead of time. They were required to write a draft experimental protocol and submit it on LabArchives before the start of their experiment. A subfolder was created for protocols under each experiment folder. The first activity on the experiment day was protocol review by the instructor or the teaching assistant (TA). Students were typically asked about the concepts behind the experiment, rationale for the experimental steps, and an explanation of calculations and data analysis that they intend to do after data acquisition. Students and the instructors/TA collectively revised the experimental protocol on LabArchives. After the protocol was finalized, the instructor/TA approved it electronically. Since LabArchives maintains a record of changes made along with time stamp and user identity, it was easy to track all the changes that were made to the protocol. Students can see in real time how their protocol has evolved from an initial draft to the final form. Pedagogically, protocol writing is an exercise in translating theoretical concepts to an experimental procedure. The collective revision of protocol by students and instructor lends well to hands-on, inquiry-based learning.[17] Unlike PLNs, LabArchives allows for multiple revisions and the final version is clear and legible. The protocol review exercise takes about 30 minutes.

### Hands-on lab work and data recording

Students performed the experiment according to the revised protocol. Data was directly recorded in LabArchives by students. Machine-acquired data was transferred from the lab equipment (such as chromatography data) through a storage device (such as a flash drive) and manually uploaded to LabArchives by students. LabArchives does not have the functionality for real-time data entry from lab equipment. All information that students will need to do an experiment was ready for download from LabArchives. LabArchives provides a robust audit trail of changes made to data entry, which allows the instructor to review data change history and access metadata. Instructors can view data entry in real time to monitor progress of the experiment. This allows the instructors to identify mistakes and intervene immediately rather than ponder what could be done differently after the experiment has been completed. LabArchives thus facilitates better engagement between the instructor and students through online contact in addition to in-person interactions.

### Data sharing and collaboration

Each experiment was done by two student teams during any given week, but the teams had different experimental conditions. Students were required to share data between teams for comparative data analysis. LabArchives allows teams to selectively share data with other teams. Students can now readily share large data sets without the need for photocopies or sending data sets and PLN pages as email attachments. Since data sharing also leaves an audit trail, the instructor can check if data is being shared in a timely manner. Because students know the teams they need to share the data with, it is also possible to schedule data sharing ahead of time for the entire course.

### Data integrity using an ELN

Data integrity is of supreme importance in scientific investigations, and the validity of new scientific knowledge is dependent on the quality of data that is generated. Elements of data integrity are best defined in the Food and Drug Administration’s (FDA’s) guidance on data integrity requirements, which state that all scientific data should be attributable, legible (and long-lasting), contemporaneously recorded, original, and accurate (or ALCOA).[24] ELN permits full life-cycle data management, from creation to archiving, while incorporating all aspects of ALCOA. LabArchives uses exclusive login for each student to access their lab notebook. Instructors (as account administrators) have the ability to restrict access or terminate users as needed. Users can retrieve lost passwords through a secure password retrieval process using the email address linked to their account. User logins are recorded and archived, which can be retrieved by the instructor. Therefore, any entry made in LabArchives is attributable to the user making the entries. Since data is directly entered or uploaded in LabArchives, all data is legible, unlike in PLNs which tend to have scratched out and overwritten data.

According to the FDA guidance, audit trail is defined as “secure, computer-generated, time-stamped electronic record that allows for reconstruction of the course of events relating to the creation, modification, or deletion of an electronic record.”[25] Any entry or upload in LabArchives will have an audit trail — i.e., user identity and time stamp for all entries, modifications, deletions, etc. — and will be recorded and available for audit by the instructor. Students were allowed to modify data, but modifications needed to be explained and justified. The instructor was able to see the original data entry and the changes that were made. Also, LabArchives Classroom Edition provides secure and redundant data storage in the cloud through primary and disaster recovery servers, thus archiving the original data permanently. Therefore, by using LabArchives we were able to preserve the originality of data.

Students were required to enter data as it was generated while doing the experiment. Thus, all data entries needed to be made during the lab period or shortly afterwards. After data entry, students submitted their lab notebook pages for review, and the submissions were time stamped. Any data submitted late was considered invalid. Thus, using LabArchives we were able to ensure that data was recorded contemporaneously (or simultaneously) with the experiment. Data generated in the bioprocess engineering lab course had a mix of computer-generated data which were uploaded to LabArchives and non-computer-generated data that were entered manually. Accuracy of computer-generated data was confirmed through a combination of LabArchives' audit trail and a time stamp on the computer on which the data was generated. Accuracy of non-computer-generated data was confirmed manually by random spot checks by the TA or the instructor. Thus, using an ELN enables superior data integrity as defined in ALCOA with much less effort than is possible through PLNs.

### Assessment of good documentation practices (GDPs) through the ELN

The ability to grade lab notebook pages and send feedback to students through LabArchives was helpful in assessing students’ good documentation practices. LabArchives is cloud-based and did not require instructors to take notebooks from students for grading. Instructors added comments, highlighted mistakes, and explained grading directly in the notebook, which was visible to all team members. Given the limited room available in a PLN, confusion often arises due to illegibility of feedback. Since feedback was communicated to students instantly, they could implement the feedback in their next ELN entries. As students became familiar with ELN, their average grade for GDPs improved. A recent study on the use of LabArchives in an upper-level biomedical engineering lab course reported improvement in students’ documentation and communication skills when using ELN, compared to PLN.[26]

Student competency in GDPs were graded according to the rubric given in Table 2. The rubric was designed to quantify the mastery in attributes important to GDPs and learning. The process of collaborative protocol revision with the instructor/TA was weighted highest because this is the step where students’ conceptual understanding of the experiment is challenged, and it presents many teaching opportunities. Raw data entry was weighted next highest. This attribute measured the level of mastery in recording data compliant with ALCOA, including good documentation practices. Draft protocol and the list of objectives measured the students’ level of preparation for the experiment. Therefore, using ELN, students were trained in GDPs, which is crucial for data reproducibility and reliability.[5]

Attribute % contribution to ELN grade Competencies measured Table 2. Rubric for assessing good documentation practices using ELN (Note that ELN use contributed to 20% of the lab course grade.) Draft protocol 16.5 Draft version of complete protocol is submitted before the lab class begins. All obvious steps are covered in the protocol, and the protocol reflects some understanding of theory behind the experiments. Objectives 16.5 Check if experimental objectives are clearly stated, preferably as a bullet point listing. Revised protocol 42 Students actively participated in collaborative revision of their draft protocol with the instructor/TA. Arguments for experimental steps were strong. Raw data and good documentation 25 Check if all raw data was compliant with ALOCA.

## References

1. Rudolphi, F.; Goossen, L.J. (2012). "Electronic laboratory notebook: The academic point of view". Journal of Chemical Information and Modeling 52 (2): 293–301. doi:10.1021/ci2003895. PMID 22077095.
2. Kloeckner, F.; Farkas, R.; Franken, T. et al. (2014). "Development of a prediction model on the acceptance of electronic laboratory notebooks in academic environments". Biomedizinische Technik 59 (2): 95–102. doi:10.1515/bmt-2013-0023. PMID 24225123.
3. Riedl D.H.; Dunn, M.K. (2013). "Quality assurance mechanisms for the unregulated research environment". Trends in Biotechnology 31 (10): 552–4. doi:10.1016/j.tibtech.2013.06.007. PMID 24054820.
4. Tachibana, C. (2014). "The paperless lab". Science 345 (6195): 468–70. doi:10.1126/science.345.6195.468.
5. Collins, F.S.; Tabak, L.A. (2014). "NIH plans to enhance reproducibility". Nature 505 (7485): 612–3. PMC PMC4058759. PMID 24482835.
6. Rosenberg, D.M.; Horn, C.C. (2016). "Neurophysiological analytics for all! Free open-source software tools for documenting, analyzing, visualizing, and sharing using electronic notebooks". Journal of Neurophysiology 116 (2): 252–62. doi:10.1152/jn.00137.2016. PMC PMC4969392. PMID 27098025.
7. Nussbeck, S.Y.; Weil, P.; Menzel, J. et al. (2014). "The laboratory notebook in the 21st century: The electronic laboratory notebook would enhance good scientific practice and increase research productivity". EMBO Reports 15 (6): 631–4. doi:10.15252/embr.201338358. PMC PMC4197872. PMID 24833749.
8. Voegele, C.; Bouchereau, B.; Robinot, N. et al. (2013). "A universal open-source electronic laboratory notebook". Bioinformatics 29 (13): 1710–1712. doi:10.1093/bioinformatics/btt253. PMID 23645817.
9. Barillari, C.; Ottoz, D.S.M.; Fuentes-Serna, J.M. et al. (2016). "openBIS ELN-LIMS: An open-source database for academic laboratories". Bioinformatics 32 (4): 638–640. doi:10.1093/bioinformatics/btv606. PMC PMC4743625. PMID 26508761.
10. Machina, H.K.; Wild, D.J. (2013). "Electronic laboratory notebooks progress and challenges in implementation". Journal of Laboratory Automation 18 (4): 264–8. doi:10.1177/2211068213484471. PMID 23592569.
11. Rubacha, M.; Rattan, A.K.; Hosselet, S.C. (2011). "A review of electronic laboratory notebooks available in the market today". Journal of Laboratory Automation 16 (1): 90–8. doi:10.1016/j.jala.2009.01.002. PMID 21609689.
12. Kanza, S.; Willoughby, C.; Gibbins, N.; Whitby, R.; Frey, J.G.; Erjavec, J.; Zupančič, K.; Kovač, K. (2017). "Electronic lab notebooks: Can they replace paper?". Journal of Cheminformatics 9: 31. doi:10.1186/s13321-017-0221-3.
13. Walsh, E.; Choi, I. (2013). "Using Evernote as an electronic lab notebook in a translational science laboratory". Journal of Laboratory Automation 18 (3): 229-34. doi:10.1177/2211068212471834. PMID 23271786.
14. Bonham, S. (2010). "Whole Class Laboratories with Google Docs". The Physics Teacher 49: 22. doi:10.1119/1.3527749.
15. Guerrero, S.; Dujardin, G.; Cabrera-Andrade, A. et al. (2016). "Analysis and Implementation of an Electronic Laboratory Notebook in a Biomedical Research Institute". PLoS One 11 (8): e0160428. doi:10.1371/journal.pone.0160428. PMC PMC4968837. PMID 27479083.
16. Frey, J.G.; Milsted, A.; Michaelides, D. et al. (2013). "MyExperimentalScience, extending the ‘workflow’". Concurrency and Computation 25 (4): 481–496. doi:10.1002/cpe.2922.
17. Hall, M.L.; Vardar-Ulu, D. (2014). "An inquiry-based biochemistry laboratory structure emphasizing competency in the scientific process: A guided approach with an electronic notebook format". Biochemistry and Molecular Biology Education 42 (1): 58-67. doi:10.1002/bmb.20769. PMID 24376181.
18. Johnston, J.; Kant, S.; Gysbers, V. et al. (2013). "Using an ePortfolio system as an electronic lab notebook in undergraduate biochemistry and molecular biology practical classes". Biochemistry and Molecular Biology Education 42 (1): 50-57. doi:10.1002/bmb.20754.
19. Weibel, J.D. (2016). "Working toward a Paperless Undergraduate Physical Chemistry Teaching Laboratory". Journal of Chemical Education 93 (4): 781–784. doi:10.1021/acs.jchemed.5b00585.
20. Kanare, H.M. (1985). Writing the Laboratory Notebook. American Chemical Society. pp. 150. ISBN 9780841209336.
21. Giles, J. (2012). "Going paperless: The digital lab". Nature 481 (7382): 430–1. doi:10.1038/481430a. PMID 22281576.
22. Butler, D. (2005). "Electronic notebooks: A new leaf". Nature 436 (7047): 20–1. doi:10.1038/436020a. PMID 16001034.
23. Pain, E. (26 July 2016). "Career advice highlights from the EuroScience Open Forum". Science. American Association for the Advancement of Science.
24. "Guidance for Industry: Electronic Source Data in Clinical Investigations" (PDF). Food and Drug Administration. September 2013. Retrieved 22 June 2017.
25. "Guidance for Industry: Data Integrity and Compliance with CGMP" (PDF). Food and Drug Administration. April 2016. Retrieved 22 June 2017.
26. Okon, M.D.; Nocera, T.M. (2017). "Electronic Lab Notebooks Impact Biomedical Engineering Students’ Quality of Documentation and Technical Communication". Proceedings from the 2017 ASEE Annual Conference & Exposition 2017.

## Notes

This presentation is faithful to the original, with only a few minor changes to grammar, spelling, and presentation, including the addition of PMCID and DOI when they were missing from the original reference.