Nanocontainers, single-stranded DNA and fluorescently labelled lipids enable researchers to perform 42,000 chemical experiments simultaneously. The new technology saves running time, human input and large quantities of materials. According to a researcher, it is like developing a great recipe.
Researchers from several universities in Denmark have collaborated in developing a new way of carrying out chemical experiments.
Instead of performing the experiments in flasks and test tubes one at a time, the researchers can use nanocontainers with single-stranded DNA fragments to execute 42,000 experiments simultaneously – and in just under 1 hour.
This saves not only time in the laboratory but also large quantities of materials.
According to the researchers, the new technology has the potential to change the procedures for many experiments and screenings.
“Performing thousands of experiments usually requires using large quantities of materials, human resources and lots of time. This revolutionary technology saves on all three, so experiments and randomised screenings can be carried out in parallel,” explains the leader of the research, Nikos Hatzakis, Associate Professor, Department of Chemistry, University of Copenhagen.
The research has been published in Nature Chemistry and included the group of Stefan Vogel, Associate Professor, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense.
Chemical experiments are like cooking classy cuisine
Nikos Hatzakis uses cooking as an analogy in explaining the new technology.
For example, making a tasty tomato sauce for pasta requires mixing ingredients such as garlic, tomato, salt, pepper and basil.
However, there are different mixing options.
You can start with garlic, then the tomatoes, then salt, pepper and finally the basil. Alternatively, you can try salt and pepper first, then the basil and finally tomatoes and garlic.
The sequence influences the results.
“Chemistry is similar. If you have six ingredients, mixing them differently will produce different results. In addition, they can be mixed in 720 ways, so performing experiments to make every conceivable mixture based on the order in which they are added would take a very long time and require lots of materials,” says Nikos Hatzakis.
Nanoscale experiments
To avoid this, the researchers in Denmark developed lipidic nanocontainers that are less than a thousandth of a human hair in width.
One target nanocontainer can be used for mixing the materials and other nanocontainers for each material.
The target nanocontainers for mixing have identity-encoding barcodes corresponding to each DNA-encoded nanocontainer for each material. When a nanocontainer with one material comes in contact with the target container, the two matching fragments of DNA zip like a zipper, and the contents of the nanocontainer with the material are emptied into the target container.
The researchers created a set-up that enables 42,000 target nanocontainers per mm2 of space.
Each container has six freely diffusing populations of cargo liposomes that can be merged with DNA fragments from each nanocontainers with its own chemical material.
The researchers put the droplets from the nanocontainers with the materials onto the lab-on-a-chip with the target containers, and the materials are mixed completely randomly.
“The beauty of this process is that we can perform thousands of experiments simultaneously and all in 1 mm2. Each nanocontainer comprises its own experiment,” explains Nikos Hatzakis.
Artificial intelligence maps the mixing sequence
But the story doesn’t end here.
The materials are mixed randomly, but how can the researchers identify how they were mixed?
To solve this, the researchers developed a method to determine instantly how the ingredients were mixed in each of the 42,000 nanocontainers.
Each lipid nanocontainer with materials is equipped with fluorescent markers, and the researchers use different combinations of red, blue and green for each container.
The researchers then use images of the experiments and artificial intelligence to map the thousands of nanocontainers, determining very precisely the order of mixing in each container.
“We can analyse 42,000 events in 1 second. Fluorescence microscopy techniques enable us to save huge amounts of time in determining the mixing order. All the aspects of this technology are part of this revolution,” says the researcher who did most of the experimental work behind the study, Mette Galsgaard Malle, PhD, who is carrying out research at Harvard University.
Useful in different types of experiments
Nikos Hatzakis envisions many fields in which this technology can save both time and resources.
For example, researchers might want to assemble genetic building blocks into a DNA strand for use in many contexts, such as medicine.
Using the technology, researchers can assemble DNA building blocks in thousands of ways using minimal quantities of materials, very few laboratories and just 1 hour to carry out the entire experiment.
Another possible application is in screening various protein–ligand interactions. Various ligands can be placed in the other nanocontainers and mixed in different ways, and researchers can determine how they interact with the protein when the order of the ligands is changed.
“We are already talking to industry, which sees great potential in our invention,” adds Nikos Hatzakis.
