Better Late Than Never, but Never Late is Better: Enabling Molecular Biology Research with Facilitated Workflows

In his 1748 essay “Advice to a Young Tradesmen,” Ben Franklin made what is now the timeless statement that “Time is money.” As researchers across both academia and industry are faced with numerous tasks and often use time-consuming protocols that can quickly become difficult to manage, it is important to remember that the time we do have should be spent wisely and not wasted. In consideration of how we as scientists strive to use our precious time to maximize our overall impact on respective scientific fields, it is especially important to be aware and look for replacements of legacy methods. We should be using more modern technologies that can provide clear time benefits.

In practice, this means selecting the best techniques and tools that work in synergy—not only giving you the most accurate and reproducible results, but also making the most of your time. Adopting and leveraging novel technologies and modern approaches to classical methods you might currently use can sometimes be uncomfortable. However, these methods demand consideration given their benefits. For example, lab coats are no longer washed by hand, but rather by a washing machine. Along these lines, routine traditional methods that require long set up and run times, such as agarose gel electrophoresis, should come under scrutiny. We are no longer performing DNA electrophoresis using starch, so why not move beyond manually pouring agarose gels and leverage the innovations available today?

If Ben Franklin were alive today, he would argue that the use of a modern molecular biology products such as Invitrogen E-Gel precast agarose gels and FastDigest Restriction Enzymes saves money through more efficient use of time. These are modern molecular biology products that greatly simplify restriction digestion and agarose gel electrophoresis, respectively. Use of modern products like these means less time spent on trivial tasks and more time exploring new ideas and more rapid data generation for inclusion of critical grant proposals or publications. For example, imagine not waiting for a gel to cool and set, and instead getting to run one more (or several!) gel in a last-minute experiment.

Specifically, use of Invitrogen E-Gel precast agarose gels and FastDigest Restriction Enzymes in a cloning experiment can deliver results 6x faster than when using conventional restriction enzymes and pouring your own agarose gels. This can mean up to 2 hours of time savings. Let’s break down where this time savings comes from in restriction digest of your DNA samples:

Taking a closer look at just the agarose gel portion of this cloning workflow further illustrates how this time savings is delivered.

• Preparing your gel – (~45 mins savings)
  • Precast agarose gels are ready to run, out of the box.
  • Preparing a self-poured homemade gel involves buffer preparation, dissolving of agarose, cooling of agarose, and solidification of the gel.
  • This step alone provides ~45 mins that could otherwise be used for result analysis, or performing a subsequent experiment – instead of being stuck waiting for agarose to set.
• Gel loading and run time – (~57 mins savings)
  • Precast gel runs can be loaded and a run completed in as little as 13 mins.
  • Traditional agarose gel setups require up to 1 hours, 10 minutes, to complete a run [2].
  • While hands-off time, this is a significant time savings advantage because it allows you to get your results 6x faster.
• Visual analysis of gel – (~14 mins savings)
  • Precast gels can be imaged in <1 min using the Power Snap Plus system.
  • Conventional gels require staining with ethidium bromide, washing, and imaging in a separate system, which takes ~15 mins.
• Cumulatively, time saved by using precast gels alone equates to approximately 2 hours saved, per gel.

As a proof-point that the time and skill required to pour your own gels is not exaggerated, there are peer-reviewed publications that specifically make note of the time and care required to obtain results when pouring your own gels. To put this time savings into perspective, the two hours needed for a single experiment using self-made gels could be used to complete 10-12 gel runs when using E-Gels, significantly improving your efficiency. These 2 hours of efficiency can also be thought of in a very tangible way using financial estimates based on your lab’s labor costs. To extend this even further, if the use of E-Gels can save two hours per day and this is done daily, this extrapolates to 10 hours per week and 40 hours per month. This alone can justify the use of precast gels.

But what about other intangible costs? For example, if you stick with pouring your own gels and traditional setups can you:

• Progress your science as fast as you want to, or as quickly as your competitors are progressing theirs?
• Explore that crazy idea you have, that could be genius, but requires another gel to be run?
• Avoid spending even more time training your staff on how to pour a gel like the rest of the lab members do?
• Stop repeating gels to get the reproducibility you need to trust your results?

Thermo Fisher Scientific believes that your time is valuable and provides you with the systems, consumables, and supporting workflows to make the most of it to progress your molecular biology research.

Industry leading E-Gel Power Snap Plus electrophoresis system integrates rapid nucleic acid separation with a high-resolution camera for gel analysis to create an all-in-one system where you simply load, run, and visualize nucleic acid gels. The E-Gel Power Snap Plus utilizes E-Gel precast agarose gels that:

• Are provided in a ready-to-use format and does not require any additional gel preparation.
• Exhibit sensitive and rapid detection of DNA or RNA.
• Are provided in a wide variety of configurations in agarose concentrations and well numbers.
• Include SYBR Safe DNA stain options that offer users safety benefits, relative to ethidium bromide.

FastDigest Restriction Enzymes also help save your valuable time by greatly simplifying DNA digestion through several inherent features:

• All enzymes exhibit 100% activity in a single buffer, which eliminates the need for sequential buffer digestions.
• Rapid digestion times eliminate the need for overnight digestions and resulting star activity.
• Buffer is 100% compatible with downstream DNA/RNA modifying enzymes such as ligases, phosphatases, kinases.
• Digestion buffer can be loaded directly onto agarose gels.

Thermo Fisher Scientific provides FastDigest Restriction Enzymes that enhance DNA digestion and streamline subsequent downstream operations. The all-in-one E-Gel Power Snap Plus electrophoresis system that can run and visualize nucleic acid gels in fraction of the time of traditional agarose gel electrophoresis.

These technologies can provide time saving improvements that can be applied to any application using restriction enzymes or agarose gel electrophoresis. Even the most current of applications, including CRISPR-mediated genome editing and development of novel molecular assays to detect pathogens of interest, are still sometimes done using self-poured gels, but could benefit from workflow improvements using E-Gels [1,3].

If you’re not already using innovative and modern molecular biology tools like those discussed here, you might need to ask yourself what your time is worth and if you’re ready to work smart, not just hard. Remember, there’s a reason washing machines replaced washboards to make those lab jackets clean and white!

1. Bhattacharya, D., Van Meir, E.G. A simple genotyping method to detect small CRISPR-Cas9 induced indels by agarose gel electrophoresis. Sci Rep 9, 4437 (2019). https://doi.org/10.1038/s41598-019-39950-4.
2. Mohammad, N., Talton, L., Hetzler, Z., Gongireddy, M. & Wei, Q. Unidirectional trans-cleaving behavior of CRISPR-Cas12a unlocks for an ultrasensitive assay using hybrid DNA reporters containing a 3′ toehold. Nucleic Acids Res (2023). https://doi.org/10.1093/nar/gkad715.
3. Choi, C. W., Hyun, J. W., Hwang, R. Y. & Powell, C. A. Loop-mediated isothermal amplification assay for detection of Candidatus liberibacter asiaticus, a causal agent of citrus Huanglongbing. Plant Pathol J (Faisalabad)34, 499–505 (2018). https://doi.org/10.5423/PPJ.FT.10.2018.0212.