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New Microfluidic Device Creates Equally Sized Nanodroplets

One drop with the volume of a millionth of a litre is actually not extremely large and does not even resemble like something that can be used for a lot of things. However, the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw developed a simple device capable of dividing microdroplet into a group of nanodroplets that are all of the same size. Henceforth, the vital genetic material and chemicals present in a single microdroplet can be the initial point of hundreds of experiments or they can also be stored in the form of nanodroplet libraries.

Until recently, droplets developed in sophisticated microfluidic devices or by electronic pipettes varied in quantity by a dozen or even several dozen percent or more. A device developed at the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) in Warsaw puts a stop to all inaccuracies and creates droplets of virtually matching volume. The droplets are calculated in nanolitres (billionth parts of a litre). The simple design of the device allows it to be used, for instance, as the tip on a pipette. The construction of the devices is a vital step in the production of microfluidic systems, which are set to transform chemistry similar to what integrated circuits did with electronics.

In modern microfluidics droplets are produced by apparatus that is either more or less complex, in processes carefully controlled by computers. Our idea was different: we decided to transfer control of the formation of droplets not to devices, but to physics itself. However you look at it, physics still has several billion years more experience than we do in this field, doesn't it?

Prof. Piotr Garstecki (IPC PAS).

Generally, microfluidic systems are constructed by permanently gluing together two plates made from transparent plastic (polycarbonate). One plate is covered with a network of accurately designed and extremely thin grooves on the side that is glued. After sticking together the plates, these grooves create channels into which a carrier liquid, mostly oil, can be forced. Adding a second liquid that is immiscible with the liquid carrier, e.g. a water solution, into the system’s interior that has been developed in this way, leads to the production, transportation, splitting, and combination of droplets whose contents are mixed.

The Holy Grail of microfluidics is to create a laboratory of a size similar to modern integrated circuits capable of carrying out complex chemical and biological experiments. In other words, a lab on a chip. This is the goal, because at the moment what we have is rather... a chip in a lab. Current microfluidic systems can already do a lot, their dimensions are small, but for such a plate to work, it has to be surrounded by syringe pumps, computers controlling flow, all in a tangle of tubes. Our device eliminates a large part of this cumbersome and expensive infrastructure.

Dr. Filip Dutka (IPC PAS; Faculty of Physics, University of Warsaw)

The device developed at the IPC PAS, commissioned by Curiosity Diagnostics, together with a grant from the Foundation for Polish Science and the European ERC Starting Grant, is basically a channel comprising a meticulously designed geometry. Introduction of the sample fluid from one side, allows it to travel through an outlet designed in a manner that when the appropriate amount of liquid has travelled through it, surface tension forces naturally tend to close the surface. This occurs at the same time on every single occasion. Due to this, each nanodroplet breaking from the outlet always contains the same volume. Prof. Garstecki's group used varied copies of the new instrument and developed a series of droplets ranging from ca. 0.5 to ca. 50nL.

Our device creates nanodroplets at a rate of several dozen per second, which is slightly slower than in traditional, controlled techniques. The number of droplets is smaller, but their quality has increased. Tests have shown that the size of the nanodroplets practically does not depend on the flow rate or viscosity of the sample liquid and a given version of the device always generates droplets of the same size. It's truly amazing that in terms of even a ten-fold difference in flow velocity, the volumes of the droplets differ from each other by only a few percent. This means that the user has complete freedom in the implementation of the experiment, and the result is always exactly in compliance with the designed protocol.

PhD student Adam Opalski, a biotechnologist from the IPC PAS.

The new device manufactured at the IPC PAS does not contain moving parts, does not get worn-out, and requires no power. The devices used in microfluidic systems reduce the demand for their accompanying infrastructure, which should speed up the distribution of microfluidic equipment. In a few years time, patent pending will also be extensively available in the form of tips for a pipette.

Dividing even the tiniest amounts of liquid into nanodroplets makes room for future research perspectives. Instead of just carrying out only one experiment on a microdroplet, it will now be possible to perform an increasing number of measurements in hundreds of individual experiments. The preciseness of statistical analysis will increase, so also the certainty of the results of diagnostic and laboratory tests. One specific area of application refers to the fact that the nanodroplets suspended in the liquid carrier do not tend to blend. Hence, it is indeed an easy task to use the microfluidic device for creating a long lasting and easy-to-store library of nanodroplets and numbering thousands of droplets with valuable biological or chemical substances. The task is easy as one just has to dip an electronic pipette with a proper tip in oil, press the button, and then wait.

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