September 9, 2021
Jack Silver, Applications Specialist
Using checklist technology to improve chromatography and lab operations
The use of time-proven
checklist technology is one fantastic way to improve chromatography results while saving time, trouble, and money in the lab. I learned this from my training as a private pilot, where it was hammered in from Day 1 that properly constructed, well executed checklists (pre-flight, in-flight, and post-flight) are essential to a safe and efficient flying experience. Heavy emphasis was placed on the fact that human memory alone is notoriously unreliable when it comes to performing multi-step procedures.
“Checklist – (noun). A list of items required, things to be done, or points to be considered, used as a reminder." [Oxford English Dictionary]
Checklist technology in the field of aviation originated in 1935 after the crash of a Boeing 299 experimental aircraft where the subsequent investigation showed it was a completely avoidable loss, caused by a single flight control clamp (the elevator gust lock) not being removed prior to takeoff.  This one small mistake resulted in two fatalities, three others injured, and total destruction of the aircraft.
More recently the use of checklist technology in other life-and-death environments, such as surgeries in hospitals, and in numerous non-life-threatening business and technology applications, has been well illustrated in Atul Gawande's 2010 book,
The Checklist Manifesto: How to Get Things Right. The book was inspired by the author reading a story about a young child who survived a fall into a frozen pond and then discovering the physician who saved her relied heavily on checklists. 
Checklists today are found everywhere, for every activity in which one person (or a team) wishes to ensure the quality and consistency of a procedure by eliminating—or greatly reducing—the errors associated with relying on human memory, such as forgetting a critical step. The key to checklist technology is the fact that
a checklist, much like an elephant, never forgets. A process can still fail, however, by inattention, misinterpretation, or non-compliance with the documented steps, but this is a different situation, one that is easier to identify and manage as compared to having no checklist at all.
Well, then, if we are going to rely on a checklist, how do we know the checklist itself is “reliable"? Checklist quality is certainly critical to success, and the best checklists have the following characteristics:
Person(s) most knowledgeable. The most effective checklists are developed by the people who are most closely involved in running the target process, and who are fully accountable for the results, that is, the “engagement" factor.
Comprehensive. The checklist must contain the
complete set of steps required for the target process; key steps cannot be left out. A checklist item can be an action (to do), a cross-check, verification, important note, or reminder.
Very explicit. A fully developed checklist does not leave anything to the imagination; it does not rely on the operator knowing, recalling, filling in gaps, or doing anything else beyond what is explicitly shown on the list.
Clear and accurate. Each step on a checklist must be technically accurate. The wording of each step should be reviewed and crafted in such a way that ambiguity is eliminated.
Relevance/importance. An efficient checklist must not be overloaded with unnecessary, irrelevant, or unimportant steps. If an item on the list does not contribute significantly to the quality, conformance, and productivity of the process, that item should be deleted.
Correct sequence. All items on a checklist must be in the proper sequence, especially where one step depends on an earlier step. In addition to the benefit of never forgetting a step, checklists add value and prevent errors by documenting the correct sequence of the process.
Customization. Checklists that are “store-bought," or that originate from abstract sources far removed from the actual field of battle, are less likely to be used on a daily basis; they are also less likely to be updated by the team. To maximize the adoption of the checklist, tailor it to suit the facility, the process, and working style of the people involved.
Validation. Checklists must be beta-tested by having key personnel review and/or use them exactly as-written with the goal of detecting errors or omissions, and revising as needed until it is proven to be complete and accurate in an actual production environment.
Self-sufficient. Ideally someone new to the target process should be able to run it correctly using only the checklist as written and with little or no special training. In fact, a good way to test the quality of a checklist is to give it to someone unfamiliar with the process and see how it is perceived, interpreted, and executed.
Checklist length. Checklist length is not important so long as the above guidelines are followed; that is, nothing important is omitted, and nothing irrelevant is included. So long as each item on a checklist is well justified, shorter is not better than longer. Remember that a well-designed checklist acts like a portable and highly practical “knowledge base."
Checklist maintenance. Checklists are living documents that must be kept current in the face of changing conditions. For example, when an error occurs in a process and the problem is investigated, a new checklist item may need to be added, or an existing item may need to be modified or deleted.
Checklists in the chromatography lab can be used to ensure an instrument is set up and functioning properly before consuming samples, solvents, analyst time, and other resources. Although a checklist takes time to develop, it saves that much time and more once it is implemented, as it prevents the errors that cause samples to be lost, and that force an analyst to re-run a procedure. And in multi-user environments especially, solvents and settings may have been changed by a previous user, and so it is smart to verify before each run that the instrument is ready for a specific purification.
Checklist examples. The excerpts below are intended to show the types of things that might be included on checklists before, during, and after a purification. As discussed earlier, each operator or lab manager would develop their own specific and comprehensive checklists suited to the way their lab works.
- The purification strategy is evaluated and defined in advance.
- List the solvents, samples, and columns required.
- Ensure all solvents are in properly labeled containers.
- Solvent lines from the instrument are routed to the correct solvent containers.
- Tip: Use colored tape to distinguish solvent lines for non-polar compounds (e.g., hexane/ethyl acetate) and polar compounds (e.g., dichloromethane/methanol).
- Visually confirm the solvent containers are full.
- Tip: Do not rely on built-in solvent management features alone; check visually.
- Verify the waste containers are empty.
- Note: Although most Teledyne ISCO systems will automatically stop the pumps if the waste containers are full, this still results in the purification process being stopped until the situation is resolved.
- The correct column type for the purification is identified and installed.
- The appropriate solvents are selected on the system interface.
- Reminder: Choosing a column causes default solvents to be selected. Nevertheless, make sure the correct solvents are displayed in the PeakTrak interface and check again that the solvent lines are routed to correspond correctly.
- Prime the solvent lines. This includes autosampler wash station and carrier solvent for a mass spectrometer. Make sure the carrier solvent is full if a mass spectrometer is being used.
- The correct purification method is loaded and modified as needed, including wavelengths (UV-Vis), and correct mass spectrometer settings (masses, ionization method, split ratio).
- Verify gas supply (usually nitrogen) for any ELSD or mass spectrometers.
During the run/equilibration:
- At equilibration, and before the sample is injected, ensure the system is running correctly.
- Verify the system shows back pressure. A lack of back-pressure suggests a leak somewhere.
- Verify injection (solid load cartridge, or make sure correct vial injected from an AutoSampler)
Perform post-run steps to make the system is ready for another user or for a subsequent run.
- If the peak has eluted, use the “Fast Forward" button to finish the run.
- Allow the instrument to clean the flow cell, pumps, and optional detectors.
- If solvent modifiers or buffers were used, wash them out unless they will immediately be used for another run.
- Tip: This lengthens column life and prevents precipitates in cases where another user needs a solvent without the modifier. For example, a sodium phosphate buffer precipitates and can damage the pumps if the next user needs to pump methanol through the system.
We hope this information encourages more users to develop practical checklists for critical lab operations. Let your imagination run wild as there are no limits to the areas in which a checklist can be used to improve operations. Please do not hesitate to send us any questions or comments about this technique, or any tips or tricks you might have regarding checklists you are already using in your lab.
Until next time…
About Teledyne ISCO - Chromatography
The Teledyne ISCO Chromatography product line includes instruments and accessories for the purification of organic compounds in normal-phase and reversed-phase separations, and for bio-purification of proteins, peptides, and other biopolymers. For more articles from Teledyne ISCO, please visit our blog.
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