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BOMBAY TECHNOLOGIST
Organ-On-A-Chip
including active vascular channels, and
aerosolized
placing them in relevant organ-specific
efficacy of new drugs which may help
microenvironment.
accelerate pharmaceutical development by
Each
individual
organ-on-chip
is
composed of a clear flexible polymer -
therapeutics,
safety
and
reducing the reliance on current costly
models.
about the size of a computer memory stick
With every human breath, air enters the
that contains hollow microfluidic channels
lungs, fills microscopic air sacs called
lined by living human cells. Because the
alveoli, and transfers oxygen through a
microdevices are translucent, they provide
thin, flexible, permeable membrane of
a window into the inner-workings of
lung cells into the bloodstream. This lung-
human organs without having to invade a
blood interface recognizes invaders such
living body.
as inhaled bacteria or toxins and activates
The researchers, now, seek to build 10
an immune response.
different human organs-on-chips, to link
The lung-on-a-chip microdevice works by
them together to more closely mimic
placing two layers of living tissues -- the
whole body physiology, and to engineer an
lining of the lung's air sacs and the blood
automated instrument that will control
vessels that surround them -- across a thin
fluid
(10µm)
flow
and
cell
viability
while
permitting real- time analysis of complex
biochemical functions. [1, 9, 10, 11]
porous,
membrane
made of
polydimethylsiloxane (PDMS).
The compartmentalization of the channels
facilitates not only the flow of air as a fluid
2. Organs
which delivers cells and nutrients to the
apical surface of the epithelium, but also
2.1. Lung-on-a-Chip
allows for pressure differences to exist
Lung-on-a-chips are being designed in an
between the middle and side channels.
effort
During normal inspiration in a human’s
to
improve
the
physiological
relevance of existing in vitro alveolar-
respiratory cycle,
capillary interface model which is the
decreases, triggering an expansion of the
fundamental functional unit of the living
alveoli. As air is pulled into the lungs,
lung.
alveolar epithelium and
endothelium
It can be used for testing the effects of
environmental
toxins,
absorption
in
intrapleural pressure
the
the coupled
capillaries
are
stretched. Since a vacuum is connected to
of
45 | Bom. Tech., 62-63, 2012-13.
BOMBAY TECHNOLOGIST
Organ-On-A-Chip
physiological responses will be quicker
contour the substrate’s desired shape. (See
and more accurate. [1, 9, 10, 12, 13, 14, 15]
fig 2). A spin coat layer of PNIPA
2.2.
[poly(N-isopropylacrylamide)]
Heart-on-chip
Traditionally,
applied.
muscle
physiology
After
its
is
dissolution,
then
the
protective film is peeled away, resulting in
tissue
a self-standing body of PNIPA. The final
morphometric,
steps involve the spin coating of protective
electrophysiological, and contractility data.
surface of PDMS over the cover slip and
Furthermore,
are
curing. These Muscular thin films (MTF)
commonly completed one at a time on
enable cardiac muscle monolayers to be
cover slips of single cells, or in isolated
engineered on a thin flexible substrate of
muscle strips
PDMS. A micro contact printing technique
experiments
samples
require
to
multiple
obtain
these
experiments
was used to lay out a fibronectin “brick
Cardiomyocytes,
are
constitute
which
heart
the
cells
generate
that
the
wall” pattern on the PDMS surface
generated an anisotropic monolayer.
electrical impulses that control the heart
rate. “Heart on a chip” is a device that
After the cutting of the thin films into two
exploits muscular thin film technology –
rows
biohybrid constructs of an engineered,
subsequent placement of the whole device
anisotropic ventricular myocardium on an
in
film –
elastomeric thin
to
measure
a
with
bath,
rectangular
electrodes
teeth,
stimulate
and
the
contraction of the myocytes via a field-
a
stimulation – thus curving the strips/teeth
potential
in the MTF. The contraction experiments
propagation, and cytoskeletal architecture
were observed by looking vertically down
in multiple tissues in the same experiment.
onto the chip and monitoring the change in
The device was created using small thin
length as the strips contracted and bent up.
contractility,
combined
quantification
of
action
with
strips of tissue made from heart muscle
cells that are connected to electrodes to
stimulate contraction.
Observing the contraction response of the
tissue allows scientists to study the effect
of physiological factors or test drugs for
The design and fabrication process of this
cardiotoxicity. Replicating segments of
particular microfluidic device entails first
heart tissue makes it possible to rapidly
covering the edges of a glass surface with
measure contraction data at the tissue
tape (or any protective film) such as to
level, rather than just studying individual
cells. [2, 16, 17]
47 | Bom. Tech., 62-63, 2012-13.
BOMBAY TECHNOLOGIST
Organ-On-A-Chip
microfluidic device is designed for the
The micro-model of kidney physiology
entering blood sample. In the glomerulus’
will also feature two parallel structures –
section, the membrane allows certain
small blood vessels and the surface lining
blood particles through its wall of capillary
of the renal tubules. This aspect of the
cells, composed by the endothelium,
device will enable researchers to study the
basement membrane and the epithelial
complex interactions between these two
podocytes. The fluid that is filtered from
structures, which are normally in intimate
the capillary blood into Bowman’s space is
association inside each of the functional
called filtrate or primary urine.
units of the kidney, the nephrons.
In the tubules, substances are added to the
One
filtrate for urine formation, and some
microfluidic device’s simulation of the full
substances reabsorbed out of the filtrate
filtration and reabsorption behavior would
and back into the blood. In the PCT,
include demonstrating that the transport
complete
nutritionally
properties between blood and filtrate are
important substances takes place. In the
identical with regards to where they occur
device, this section is a straight channel,
and what is being let in by the membrane.
but blood particles going to the filtrate
For example, the large majority of passive
have to cross the previously mentioned
transport of water occurs in the proximal
membrane and a layer of renal proximal
tubule and the descending thin limb, or the
tubule cells. The second segment of the
active transport of NaCl largely occurs in
tubules is the loop of Henle where the
the
reabsorption of water and ions from the
ascending limb.
urine takes place. The device’s looping
requirements would require the filtration
channels
the
fraction in the glomerulus to vary between
countercurrent mechanism of the loop of
15%-20%, or the filtration reabsorption in
Henle.
the loop of Henle
the proximal convoluted tubule to vary
requires a number of different cell types
between 65%-70%, and finally the urea
because each cell type has distinct
concentration in urine (collected at one of
transport properties and characteristics.
the two outlets of the device) to vary
These include the descending limb cells,
between 200-400mM.
absorption
strives
Likewise,
to
of
simulate
thin ascending limb cells, thick ascending
limb cells, cortical collecting duct cells
and medullary collecting duct cells.
step
towards
proximal
tubule
validating
and
the
the
thick
The device’s design
However, the flow of blood and urine
means that renal tubular cells are exposed
to shear stresses. It also brings challenges
50 | Bom. Tech., 62-63, 2012-13.
BOMBAY TECHNOLOGIST
Organ-On-A-Chip
these tissue chips to test drug candidates
3. Kyung-Jin Jang1,et al., Wyss Institute for
and predict their safety before the next
Biologically
step, human drug studies. This approach is
Harvard University, USA
expected be more rapid and cost effective
than
those
currently
available.
Inspired
Engineering
at
4. Seoul National University, Korea; and
Children’s Hospital,
The
Harvard
Medical
National Institute of Health, pointed to
School and Harvard School of Engineering
studies that show that more than 30
and Applied Sciences, USA July 27, 2012.
percent of promising medications have
5. By Leila Gray UW Health Sciences/UW
failed in human clinical trials because the
Medicine. Seattle researchers to engineer
drugs were found to be toxic, despite pre-
kidney tissue chip for predicting drug
clinical studies in animal models. Tissue
safety
chips may offer more accurate predictions
6. Sarah C.P. Williams, The Wyss Institute,
of the side effects of potential therapeutic
Multiple organ-on-chips into a single
agents because they contain human cells.
automated instrument that tests whole-
These bioengineered devices will produce
body effects of drugs. 07/25/2012.
relevant physiological functions and will
7. Axel Günther, Sanjesh Yasotharan, et al.
reflect the complexity and diversity of
Lab Chip,(2010), 2341-2349 Received 25
living
Mar (2010), Accepted 14 Jun (2010) First
organs,
differences,
including
disease
genetic
complexity
published on the web 06 Jul 2010 .
and
8.
pharmacological responses.
Artery-on-a-Chip
Symposium
and
Workshop 2011 March 8, 2011 – The
Faculty Club, Main Floor Dining Room,
References
University of Toronto, 41 Willcocks Street
1. Dongeun Huh, Benjamin D. Matthews, et
al.“Reconstituting
Organ-Level
Lung
Toronto, Ontario M5S 1C7
9.
Dongeun Huh, Daniel C. Leslie, Benjamin
Functions on a Chip”, Science, 328 (5986)
D. Matthews, Jacob P. Fraser1, Samuel
(2010) 1662-1668.
Jurek, Geraldine A. Hamilton1, Kevin S.et
2. Anna Grasberg, Patrick W. Alford et al.
al
“A Human Disease Model of Drug
“Ensembles of engineered cardiac tissues
Toxicity–Induced Pulmonary Edema in a
for physiological and pharmacological
Lung-on-a-Chip Microdevice” SciTransl
study: Heart on a chip” Lab on chip, 24
Med 7 November (2012): Vol. 4, Issue
(2011).
159, p. 159ra147
10. Robert
Breathes
F.
Service,
New
Life
“Lung-on-a-Chip
Into
Drug
52 | Bom. Tech., 62-63, 2012-13.
BOMBAY TECHNOLOGIST
Organ-On-A-Chip
Discovery”Science 9 November 2012:
Vol. 338 no. 6108 p. 731
14.
http://en.wikipedia.org/wiki/Organ-on-achip. (Accessed Dec 2012)
11. “Human-on-a-chip may end lab animal
15. DrakeBennett, “Making Human Organs on
testing” Mumbai mirror, tech talk, Dec
a Chip” Bloomberg business week, June
2012.
27, 2012.
12. Wyss institute home page
16. Med gadget home page
http://wyss.harvard.edu/viewpressrelease/3
http://www.medgadget.com/2011/11/beat
6/living-breathing- human- lungonachip-a-
ing- heart-on-a-chip- may-revolutionize-
potential-drugtesting-alternative (Accessed
in- vitro-cardiac-studies.html
Dec 2012)
Dec 2012)
13. Red orbit-universe online
(Accessed
17. RSC-advancing chemical sciences
http://www.redorbit.com/news/health/1112
http://www.rsc.org/chemistryworld/News
727640/disease-organ-on-a-chip- model-
/2011/November/10111102.asp(Accesse
110812/(Accessed Dec 2012)
dDec 2012).
53 | Bom. Tech., 62-63, 2012-13.