Droplets on the micrometer
Bits&Chips 2, page 32-34, February 2015 (Originally in Dutch)
Author: Pieter Edelman | Translation and Edited: Robin de Bruijn
EmulTech from Eindhoven, recently launched a product to manufacture microscopic particles not with traditional bulk methods, but using microfluidics. EmulTech focuses on controlled drug
delivery.
There is a proven method to mix a fatty substance and an aqueous substance: stirring hard.
Margarine, for example, consists of small water droplets in oil; in production the two liquids are
just mixed with a mixer until very fine particles are formed. Such small beads are also
interesting for the medical sector. Drug product manufacturers use microscopic particles of
polymers, for example, for controlled release of active pharmaceutical ingredients over the
course of days, weeks or months. When the particles are injected at a specific location, they
have a highly focused and local drug release. "It has been used for decades in treating chronic
conditions. A well-known product treats schizophrenia. Also certain cancers require prolonged
treatment, or hormonal imbalances", says Robin de Bruijn. In 2009 he founded EmulTech as a
spin-off from the Eindhoven University of Technology to fabricate such spheres in a better way.
Although the pharmaceutical industry is highly interested, the field currently is still a niche. "Drug
delivery is seen as a very hot field, but in the meanwhile, it begins to cool down as it is a very
challenging field”, opts De Bruijn.
This has to do with the difficulties in the conventional production processes. Conventional
particles are prepared by stirring two liquids, for example a hydrophobic polymer and a drug in
an aqueous phase. But where this approach can yield fine margarine, the result within the
pharma world is very different. Indeed, it is an uncontrolled process whereby particles have
widely differing dimensions. In the high demanding world of drug delivery this is not acceptable.
A simple solution is filtering the beads. In a set of filters the beads with the right dimensions are
captured, but a significant portion of the produced particles are thrown out. Especially when they
are loaded with a costly drug this is very unattractive. De Bruijn gives an example "There is
already a product withdrawn from the market, because it was too expensive to produce; they
threw away one in three batches, because the result was not on spec".
Last year EmulTech launched its INFINITY
Lab system for product development
purposes, although it is also used for
production of smaller applications.
Various sizes
The idea for EmulTech emerged in 2008, following De Bruijn's thesis at the Eindhoven
University of Technology. From its inception, the company has been working to develop its
solution specifically for two applications: research and development. This led in September to
the market launch of the first two devices: the INFINITY Mini as a research tool and the
INFINITY Lab as a development tool.
The microfluidic design is not complicated. Through the main channel the first phase is pumped,
containing the polymer and drug dissolved therein. Droplets are pinched off with a stream of
water (or other liquid) out of two channels from the side. This design in itself is not new, but so
far it is not used for production purposes. The value of the solution must therefore be sought
mainly in the total system, where two liquids with the correct pumping parameters in the
microfluidic chip are forming consistent droplets, explains De Bruijn. "In these tiny dimensions,
the result is determined how you bring the liquids together. We therefore chose robust
processes and components that we combine in a smart way. You can for example add a whole
new type of pump, but within the pharma this very challenging from a regulatory view; you
actually need to become a new pump supplier."
With the INFINITY, it is possible to make particles of various sizes, depending on the process
parameters and the microfluidic chips used. "Typically they are about twenty to thirty microns;
this is ideal for controlled release and of comparable applications. But also the nanometer range
is possible thanks to our technology. There are many companies in this area that develop
products, but you're talking about such small channels, this practically produces near to nothing.
Because we have scaled to a large amount of channels already, we are at a production rate that
can be carried out on a laboratory scale."
At this moment the systems of EmulTech are still mainly applicable within R&D. "For some
markets, our system is already sufficient for full-scale production. We are working with clients in
niches where only a very little volume is needed, for example in the eye. "
But that is not the end; precisely the ability to scale up, is attractive about the technology. The
current machine uses four hundred channels together on a single chip, and can easily be scaled
up further with additional chips. That's a big difference with the current state of art, because the
mixing processes on large scale yield very different results than on a small scale.
Such scaling, however, is not currently available for EmulTech. Although there are plans, albeit
in a very different field: food. "With a company that makes coatings for the food we are in a
somewhat earlier stage, but there are plans for factories at tons-scale."
Fairly mature
Oddly enough, the microfluidics approach within the pharmaceutical industry is still a relatively
young trade. It is within the medical sector that several interesting applications have emerged in
the recent years. "But the pharmaceutical world is not familiar with it; because they are used to
the classical methods for bulk production. Pharma is fully geared to develop drug products in a
very traditional and rigid way," says De Bruijn from the experiences with his business. "There
are proteins developed as drugs now, which already have a pretty big impact. And now drug
delivery suddenly is about physics and devices, which need physicists and mechanical
engineers."
Nevertheless - or perhaps because of this – EmulTech sees a sunny future. "We're getting
requests from everywhere’ says De Bruijn "We've done a lot in Europe and the US. Now our
field of drug delivery begins to be mature, we also see a lot of interest from Asia. "
It is perhaps a strange idea; until recently it was unthinkable to produce each droplet separately.
But precisely in an area where microscopic variations can make such a big difference, the
microfluidic approach seems a hit.