An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture chip that simulates the activities, mechanics and physiological response of entire organs and organ systems, a type of artificial organ. It constitutes the subject matter of significant biomedical engineering research, more precisely in bio-MEMS. The convergence of labs-on-chips (LOCs) and cell biology has permitted the study of human physiology in an organ-specific context, introducing a novel model of in vitro multicellular human organisms. One day, they will perhaps abolish the need for animals in drug development and toxin testing.

1. Major seminar
Organ on a chip- Replacement of laboratory
animals
Submitted by
Ranjitha H.B.
P-2082 (IVRI)
Division of Veterinary Biotechnology

2. Contents
• Drug development model
• Organ on a chip
• Microfluidics
• Fabrication method
• Lung on a chip
• Human disease model
• Eye on a chip
• Gut on a chip
• Kidney glomerulus on a chip
• Liver on a chip
• Conclusion

3. The big challenge: Current drug
development model

4. Why the drug development model is broken
• Cost to develop and approve a new drug >$2.5
billion
• Cells cultured in dishes don’t function like in our
bodies
• Animal studies takes years to complete
• Innumerable animal lives are lost
• Results often don’t predict clinical response
Need better lab models that mimic
whole human organ function

5. ORGAN-ON-A-CHIP
Human cells
Structure
Environment
• Microengineered biomimetic system
• Engineer microchips containing living
human cells that reconstitute organ-level
functions
Uses:
-to test efficacy, toxicity of drugs and chemicals
-to create in vitro models of human disease

6. Microfluidics
• Science of manipulating small amounts (10–9 to 10–18 L) of
fluids in microfabricated hollow channels
• Advantages-
-It offers control of features at same size scale of living cells
-Tune dynamic fluid flows and spatiotemporal gradients
-Sample saving
Whitesides, G.M. 2006

7. Fabrication methods for microfluidic chips
Huh et al., 2011; Bhatiya et al., 2014
a) Photolithography
b)Microfluidic devices- PDMS substrate containing microchannel features
created by replica molding with a blank PDMS slab.
b) Soft lithography

8. Lung on a chip
Patton & Byron, Nat. Rev. drug discovery
AIR
BLOOD
BIODESIGN PRINCIPLES:
• Tissue-Tissue interface
• Dynamic flow
• Cyclic breathing movements
Huh et al., 2010

9. Design of lung on a chip

10. From design to device
Huh et al., 2013 Nature protocol

11. Human disease model:
Pulmonary edema in a lung-on-a-chip
Huh et al., 2012. Sci. Trans. Med.
Clinically relevant dose of IL-2 (1000 U/ml)

12. Effects of IL-2 cancer drug on lung permeability
depends on mechanical breathing motions
On chip
Vascular
leakage
model
Prediction
confirmed
In Vivo
Discovery of mechanotherapeutic
Huh et al., 2012

13. Eye on a chip
(A) Porous polystyrene shell scaffolds (5mm) (B)Scanning electron microscope (SEM) images of the scaffolds, 500 μm and 50 μm
(inset). (C) Formation of corneal stroma on scaffold pores with keratocytes and type I collagen gel (D)Confocal image of fluorescently
labeled keratocytes. Green and blue represent cytoplasmic and nuclear staining,espectively. (E) 3D patterning of green and red
HCECs on the curved scaffold surface to recapitulate human corneal and conjunctival tissues.
Seo & Huh, 2014

14. Gut on a chip
Microbial co-culture on a human intestinal epithelial monolayer
Kim et al., 2012
Gut-on-a-chip device Phase-contrast micrograph of intestinal vili
Cellbarrier

15. Human kidney proximal tubule-on-a-chip
(nephrotoxicity assessment)
Design for the human kidney proximal tubule-on-a-chip
Cell morphology
under static conditions
versus flowAnalysis of proximal tubular epithelial cell functions
Jang et al., 2013

16. Cisplatin toxicity measured in vitro
Apoptosis, as determined by TUNEL assay
Immunofluorescence views of Annexin V
Jang et al., 2013

17. Kidney glomerulus on a chip
Organ chip lined by-
•Human iPS derived kidney podocytes
•Human glomerular microvascular endothelium
Musah et al., 2017

18. Liver on a chip
Microfluidic liver sinusoid
Hepatotoxicity of diclofenac on human hepatocytes. The
drug was prepared at 100–700 mM in cell culture medium
and exposed to human hepatocytes in the microfluidic
sinusoid for 4 h ( ) and 24 h ( ).
Lee et al., 2007

19. Liver on a chip response to
acetaminophen, N-acetyl-L-cysteine
countermeasure
Viability as determined by LIVE/DEAD staining
Green – Calcein AM-stained viable cells; Red –
Ethidium homodimer-stained dead cells
Skardal et al., 2017

20. Soohee Cho & Jeong-Yeol Yoon, 2017

21. Advantages
• Replace animal models
• Study on interactions of pathogens & organ
cells, mechanism of virus infection
• To study effect of drug on target organ and
also others
• Study of toxicity of drugs and cosmetics
• To study cancer cells and produce new drugs
• Helps in pharmacological studies

22. Disadvantages of organ on a chip
• Some organ functions—cognition in the brain,
mechanical function in bone, ligaments, tendons
cannot be readily modeled on chips
• Specialized microengineering capabilities
• microbial contamination
• Chronic disease???

23. Huh, along with Donald Ingber of Harvard’s Wyss Institute,
received the Design Museum of London’s 2015 Design of the
Year award

24. Conclusion
The potential for transformative change-
As an alternative to conventional cell culture &
animal models, human organs-on-chips could
transform many areas of basic research and drug
development. They could be applied to research on
molecular mechanisms of organ development, disease
& on the interactions of the body with stimuli such as
drugs, environmental agents, consumer products and
medical devices.

25. •Thank you

26. • References
• Whitesides, G.M., 2006. The origins and the future of
microfluidics. Nature, 442(7101): 368.
• Huh, D., Hamilton, G.A. and Ingber, D.E., 2011. From 3D cell culture to organs-on-
chips. Trends in cell biology, 21(12): 745-754.
• Huh, D., Kim, H.J., Fraser, J.P., Shea, D.E., Khan, M., Bahinski, A., Hamilton, G.A.
and Ingber, D.E., 2013. Microfabrication of human organs-on-chips. Nature
protocols, 8(11): 2135.
• Esch, E.W., Bahinski, A. and Huh, D., 2015. Organs-on-chips at the frontiers of
drug discovery. Nature reviews. Drug discovery: 248.
• Bhatia, S.N. and Ingber, D.E., 2014. Microfluidic organs-on-chips. Nature
biotechnology: 760-772.
• Sung, J.H., Esch, M.B., Prot, J.M., Long, C.J., Smith, A., Hickman, J.J. and Shuler,
M.L., 2013. Microfabricated mammalian organ systems and their integration into
models of whole animals and humans. Lab on a Chip, 13(7): 1201-1212.
• Huh, D., Leslie, D.C., Matthews, B.D., Fraser, J.P., Jurek, S., Hamilton, G.A.,
Thorneloe, K.S., McAlexander, M.A. and Ingber, D.E., 2012. A human disease
model of drug toxicity–induced pulmonary edema in a lung-on-a-chip
microdevice. Science translational medicine, 4(159): 159ra147-159ra147.