Microfluidics and

Drug Delivery
A m b e r Ya s e m i n Çe l e b i

T
oday more than ever the creation volunteers are tested with novel drugs
of innovative drugs, in terms of before they are administered more
their effectiveness to disease widely, or internationally, there is still
and illness is more important than much waste of biological materials
ever. Traditional drug delivery revolves before the testing phase. With the ad-
around much patient testing and the vances of microfluidics, much of that
use of animals prior to pharmaceuti- testing can be done more cost effec-
cal companies asking for volunteers tively with the cheaper, less waste and
for their testing purposes. And though reduced amount of biological material

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 Amber Yasemin Çelebi

for chips that function with microflu- larger processes in microscale and
idics such as organs-on- a- chip and conform to sustainability since the use
labs- on -a- chip. While these technol- of materials is minimal and much test-
ogies are still rather new and their use ing on animals is reduced. Microfluidic
of biological materials at the cellular chips are also cost effective and their
level is impressive much more can be advantages seem to outweigh any dis-
done in the future of bioengineering advantages.
to determine the full impact and effec-
tiveness of these microfluidics tech- Microfluidic Chips
nologies and particularly in terms of Engineering, particularly mechanical,
developing their potential for a more has developed technologies like mi-
increased holistic understanding of crofluidics. During the 1980s the f ield
the bodily functions and in terms of of MEMS, or microelectro-mechan-
developing drugs towards this under- ical systems, was discovered which
standing. later diffused into medical and bio-
logical studies. İİİ According to the en-
Introduction gineering def inition, microfluidics is
The world of scientif ic research is get- “the study of flows that are simple or
ting smaller and smaller. No more complex, mono or multiphasic, which
do we need the large-room size labs are circulating in artif icial microsys-
to conduct research on cells for drug tems, i.e., systems that are fabricated
development because today we can using new technologies.” İV MEMS are
f it it on a chip. Lab on chip or LOC is electromechanical systems that can
the name given to such chips that are range in size f rom 1-300 micrometers.V
made up of many tiny little parts such The most common, but least known
as “f ilters, valves and mixers.” İ Micro- of MEM is the one installed in our ve-
fluidics, thus, “is the technology of flu- hicle airbags. These MEMS were f irst
id manipulation in channels with di- used in the 1980s and consists of a
mensions of tens of micrometers” and system contained on “a silicon wafer
is the effort of and used in multitude that is just a few millimeters long”, but
f ields and departments such as biolo- is powerful enough to detect when a
gy, chemistry, medicine and mechan- person has caused a collision and can
ical engineering. İİ Since these devices react to operate the airbag.Vİ
are miniature it has been necessary to
advance technology in their microfab- Microfluidics and Lab on a Chip
rication to produce the tiny channels Microfluidics can be made to be tiny
for liquid travel, such as in the one drop to f it on a chip. For this sometimes
microfluidic device. These devices are millions of microchannels made up
signif icant in the testing of many hu- of various materials are used to mea-
man and animal cells, to discover the sure microscopic fluids or specimens,
reactions in their proteins, for exam- sometimes as small as “a few picoli-
ple, and how they react to drugs in or- ters.” Vİİ “A lab-on-a-chip is a miniatur-
der to better understand cell function ized device that integrates into a sin-
to create innovative drugs for resistant gle chip one or several analyses, which
types. The benef it of these microfluid- are usually done in a laboratory; anal-
ic chips, such as LOC and organ-on- yses such as DNA sequencing or bio-
a-chip enable scientists to replicate chemical detection.” Vİİİ

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 Microfluidics and Drug Delivery

Scientif ic testing, or traditional meth- to certain drug tests. In the process

ods of research, are lacking, Eje- of preventing diseases of the lungs,
ta (2021) in that they are dependent heart, simply tissues that are diff i-
on “high batch-to-batch variations” cult to extract f rom the human body,
which contribute to “insuff icient pro- it is hard to test with and see accu-
duction rate” to also lack in “technol- rate results. Fortunately, microfluidic
ogy for fast screening of nanopartic- technology presents a revolutionary
ulate drug delivery structures with technique to ease the process of sci-
high correlation to in vivo tests.” İX entif ic research. It consists of several
Moreover, it could be argued that layers of Y-shaped channels, microflu-
simulations and testing on animals idic devices, allowing precise control
are not the best alternative that tradi- of the fluids and nanoparticles. X The
tional scientif ic research depends on. complex artif icial structure helps re-
The only actual way to understand the searchers observe the reactions and
drug’s effect on humans is to do test- processes taking place in the cell col-
ing on human cells or tissues, which ony or tissue. In this way, it is easier to
are the same as the target of the drug. monitor the delivery of the drug into
Because testing on humans is a very the target receptor and, if present,
problematic procedure as it is not spot the main source of the problem.
time-eff icient, morally problematic, To conclude, “Drug delivery technolo-
and has dangerous effects on some gy advancements can improve phar-
cases, it is generally not chosen to macological factors, including eff ica-
be carried out by researchers. Conse- cy and bioavailability, resulting in the
quently, in vitro experiments are con- discovery and development of more
ducted to observe the drug. However, effective drugs for better patient out-
in vitro experiments are not applicable comes and quality of life.” Xİ

Image 1.
Microfluidics for Drug DeliveryXİİ

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 Amber Yasemin Çelebi

Image 2. Xİİİ

Microfluidics and Organ-on-Chip versity, used organ-on-a-chip to test for

Hepatitis B virus being the f irst institu-
“An organ-on-a-chip is a microfluid- tion to test how pathogens react with
ic cell culture device created with mi- artif icial human organs. XV The artif icial
crochip manufacturing methods that liver they used was created by MIT and
contains continuously perfused cham-
Oxford as Imperial researchers, led by
bers inhabited by living cells arranged
Dr. Marcus Dorner, which would be
to simulate tissue- and organ-level
physiology. By recapitulating the mul-
then tested to f ind a drug for Hepati-
ticellular architectures, tissue-tissue tis B which currently has no cure. XVİ Not
interfaces, physicochemical microen- only were the researchers able to assess
vironments and vascular perfusion of the impact Hepatitis B has on the arti-
the body, these devices produce lev- f icial human liver, in real-time, but they
els of tissue and organ functionality were also able to determine “the virus’s
not possible with conventional 2D or intricate means of evading inbuilt im-
3D culture systems. They also enable mune responses”, an invaluable f ind
high-resolution, real-time imaging and
for drug development purposes. XVİİ The
in vitro analysis of biochemical, ge-
benef its to organ-on-a-chip include,
netic and metabolic activities of living
cells in a functional tissue and organ
as previously mentioned, smaller scale
context. This technology has great po- samples as well as less invasive testing
tential to advance the study of tissue on humans. Because Hepatitis is an
development, organ physiology and infectious disease it would be better
disease etiology.” XİV to use such technologies with human
cells on a chip instead of animals to see
In 2018, Imperial College London, in how such viruses react with drugs to
collaboration with MIT and Oxford Uni- eventually f ind a treatment.

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 Microfluidics and Drug Delivery

University College London Professor react to certain drugs and make drug
Nicolas Szita (2019) and his team stud- testing easier and less harmful to hu-
ied the ways we can make “personal- man subjects.
ized medicine a reality” and for us to
achieve this we need more “cost-ef- Microfluidics for No Ethical
fective methods that enable the rap- Concerns?
id selection of optimal nutrient intake Many new technologies come with
and/or disease treatment with a mini- their problems and concerns. Today ar-
mum of side effects.” They suggest we tif icial intelligence is paving the future
achieve this goal by using microfluidic to offer us precision in data and predic-
devices “to progress more towards an tion, but it does not come without se-
in vitro platform for health and wellbe- rious issues of ethics and concerns for
ing.” XVİİİ In vivo is conducting an exper- those who will be using it, especially
iment on an artif icial lab environment in the healthcare industry. Could it be
which is outside of a living organism, that the new technology of microfluid-
and in vivo means experimenting on ics in chips, as organs or labs, have no
living cells or tissues. ethical issues to contemplate? This is
The study suggests more use of mi- very hopeful and what is more it could
crofluidics, and also using “human also be eliminating ethical concerns in
mini-organs’’ or “organoids” as a way its path. Since lab on a chip technolo-
to test for metabolic function. Not only gy implements the lab operations on
would the use of microfluidics offer a a micro scale chip, it reduces the de-
cost effective and labor reduced option pendence on testing on animals, and
for testing of personal health it also of- thus, has the ability to erase the animal
fers less harm need for animal testing harm caused in drug tests. In this way,
and less quantities of biological materi- microfluidics not only create a more
al in the standard-sized laboratory. The precise and eff icient process of scien-
cons to this procedure are that “to date, tif ic studies but also delete the major
in vitro models are unable to simulate problem faced by ethical concerns due
the interactions and physiological re- to animal cruelty during drug testing.
sponses of individual patient’s cells to Aside f rom the ethical concerns, how-
exogenous compounds in a suff iciently ever, all technologies in their infancy
realistic and translatable way as com- come with disadvantages and draw-
pared to in vivo responses.” XİX The pro- backs that must be researched and
cess itself revolves around cells being tested to be optimized. In microfluidics
arranged in “culture devices to repli- the disadvantages could come in f irst-
cate tissue” or the system of the organ- ly not being able to observe the bigger
on-a-chip, or they can be grown f rom pattern of the drug’s effect on the hu-
patient cells that hold the phenotypes man body as a whole (side effects etc.),
and genotype of the patient. These or- and secondly, diff iculty in production
gans-on-a-chip have the potential to in a synthetic in vivo environment. The
make a more sustainable study of bio- benef its, however, are def initely relat-
engineering as well as improve overall ed to microfluidic chips being cost ef-
well-being and health for millions of fective, relatively easy to reproduce in a
people. XX For drug delivery, such mi- small space and they prevent extrane-
crofluidic chips are used to understand ous (and invasive) testing on humans
human metabolic processes as they and animals.

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 Amber Yasemin Çelebi

Image 3. XXİ

Conclusion Today microfluidics can even be seen

Microfluidic technology packs a great used in defense and against bioterror-
depth of potential drug delivery in tiny ism to aid off icers with chemical and
proportions. Tiny channels and f ilters or biological substances in the case of
that can hold a microscopic amount of toxins or poisons during warfare. A lack
fluid that is readily available to analyze of ethical issues around microfluidics
molecular level viruses, bacteria and and microfluidic chips increases the
other cells, such as proteins and DNA potential of this technology and open
and how they react with drugs is rev- up space for more possibilities in the
olutionary. Though it may sound too future where human (and animal) lives
good to be true, microfluidics enables will no longer suffer f rom the testing
testing of biological materials that pro- phase of drug development and over-
mote sustainability because they use treatment can be prevented to pro-
fewer biological materials, they cause mote well-being and health worldwide.
less harm to humans and animals be-
cause they reduce invasive testing with Endnotes
novel drugs that may cause harms un- i Bragheri, F., Vázquez, R. M., & Osellame, R.
known in the future and they occupy (2020). Microfluidics. In Three-Dimensional
Microfabrication Using Two-Photon
very little space which could enable
Polymerization (pp. 493-526). William
much more research to be conducted Andrew Publishing.
with many more microfluidic devices. ii Ibid.
Today the sector of microfluidics is in- iii Tabeling, P. (2005). Introduction to
creasing and many more companies microfluidics. OUP Oxford.
around the world are making such de- iv Ibid.
v Ibid.
vices at very little cost. While some mi-
vi Ibid.
crofluidic chips are very expensive, they
vii Team, E. (2021, April 22). Introduction to lab-
offer much more sophisticated testing.

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 Microfluidics and Drug Delivery

on-a-chip 2020: Review, history and future. Polymerization (pp. 493-526). William
Retrieved October 11, 2021, from https:// Andrew Publishing.
www.elveflow.com/microfluidic-reviews/ [3] Brogan, C. (2018, February 14). Organ-
generalmicrofluidics/introduction-to-lab- on-chip technology enters next stage as
on-a-chip-review-history-and-future/ experts test hepatitis B virus: Imperial News:
viii Ibid. Imperial College London. Retrieved October
ix Ejeta, F. (2021). Recent Advances of 4, 2021, from https://www.imperial.ac.uk/
Microfluidic Platforms for Controlled Drug news/184847/organ-on-chip-technology-
Delivery in Nanomedicine. Drug Design, enters-next-stage-experts/
Development and Therapy, 15, 3881. [4] Ciceri, D., Perera, J. M., & Stevens, G. W. (2014).
x Ciceri, D., Perera, J. M., & Stevens, G. W. The use of microfluidic devices in solvent
(2014). The use of microfluidic devices in extraction. Journal of Chemical Technology &
solvent extraction. Journal of Chemical Biotechnology, 89(6), 771-786.
Technology & Biotechnology, 89(6), 771-786. [5] Damiati, S., Kompella, U. B., Damiati, S. A.,
xi See endnote ix. & Kodzius, R. (2018). Microfluidic devices for
xii Liu, D., Zhang, H., Fontana, F., Hirvonen, J. T., drug delivery systems and drug screening.
& Santos, H. A. (2017). Microfluidic-assisted Genes, 9(2), 103.
fabrication of carriers for controlled drug [6] Demircan Yalçın, Y., Töral, T. B., Sukas, S.,
delivery. Lab on a Chip, 17(11), 1856-1883. Yıldırım, E., Zorlu, Ö, Gündüz, U., & Külah,
xiii Flow control for organ-on-a-chip H. (2021, June 23). A microfluidic device
application. (n.d.). Retrieved October 7, enabling drug resistance analysis of
2021, from https://www.bronkhorst.com/int/ leukemia cells via coupled dielectrophoretic
blog-1/flow-control-for-organ-on-a-chip- detection and impedimetric counting.
application/ Retrieved September 3, 2021, from https://
xiv Bhatia, S. N., & Ingber, D. E. (2014). www.nature.com/articles/s41598-021-92647-5
Microfluidic organs-on-chips. Nature [7] Ejeta, F. (2021). Recent Advances of
biotechnology, 32(8), 760-772. Microfluidic Platforms for Controlled Drug
xv Brogan, C. (2018, February 14). Organ- Delivery in Nanomedicine. Drug Design,
on-chip technology enters next stage as Development and Therapy, 15, 3881.
experts test hepatitis B virus: Imperial [8] Liu, D., Zhang, H., Fontana, F., Hirvonen, J. T.,
News: Imperial College London. Retrieved & Santos, H. A. (2017). Microfluidic-assisted
October 4, 2021, from https://www.imperial. fabrication of carriers for controlled drug
ac.uk/news/184847/organ-on-chip- delivery. Lab on a Chip, 17(11), 1856-1883.
technology-enters-next-stage-experts/ [9] Marques, M. P., Boyd, A. S., Polizzi, K., &
xvi Ibid. Szita, N. (2019). Microfluidic devices towards
xvii Ibid. personalized health and wellbeing. Journal
xviii Marques, M. P., Boyd, A. S., Polizzi, K., & of Chemical Technology & Biotechnology,
Szita, N. (2019). Microfluidic devices towards 94(8), 2412-2415.
personalized health and wellbeing. Journal [10] Tabeling, P. (2005). Introduction to
of Chemical Technology & Biotechnology, microfluidics. OUP Oxford.
94(8), 2412-2415. [11] Team, E. (2021, April 22). Introduction to lab-
xix Ibid. on-a-chip 2020: Review, history and future.
xx Ibid. Retrieved October 11, 2021, from https://www.
xxi Winkler, S., Grünberger, A., & Bahnemann, elveflow.com/microfluidic-reviews/general-
J. (2021). Microfluidics in Biotechnology: microfluidics/introduction-to-lab-on-a-chip-
Quo Vadis. review-history-and-future/
[12] Tiny Devices to Heal Wounds Faster and
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