20161005 Organ on a chip - SNU OPEN COURSEWARE
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Transcript of 20161005 Organ on a chip - SNU OPEN COURSEWARE
What is “Organ-on-a-chip”?
What is Organ-on-a-chip?
What is Organ-on-a-chip?
Bioengineering Mechanical engineering
http://www.edutrics.com/wp-content/uploads https://www.wired.com/2015/06/chip-mimics-human-organs-design-year/
Organ-on-a-chip
What is Organ-on-a-chip?
http://home.sogang.ac.kr/sites/nbel/Research/Pages/Cell%20Chip.aspx
Importance of Organ-on-a-chip
http://www.gartner.com/technology/home.jsp
Expecting technologies in July, 2015
The purpose of Organ-on-a-chip
Disease Model
New drug development
Huh, Dongeun, et al. Science (2010)
Chemical Drugs (신약) vs. Biologics (바이오시밀러)
http://www.hcrnetwork.com/biosimilars-market-in-the-us-2015/http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/
http://www.popsci.com/what-is-biosimilar
Biosimilar (바이오시밀러)
✓ “Highly similar” to an already-approved biological product
✓ Can save U.S. $250 billion over the next decade
http://blog.samsung.co.kr/5682http://www.enewstoday.co.kr/news/articleView.html?
idxno=609668
SAMSUNG BIOEPIS
http://news.newsway.co.kr/view.php?tp=1&ud=2016090810312972685&md=20160908103409_AOhttp://news.mtn.co.kr/newscenter/news_viewer.mtn?gidx=2016100409383584361
Drug development process
http://www.ppdi.com/About/About-Drug-Discovery-and-Development
Clinical Trial (임상시험)
New drug development
In pre-clinical research, we should test
✓ Toxicity and Efficacy✓ Test first on animal models✓ Whether it is safe to test on human
New drug development
https://www.retaildetail.eu/en/news/drogmetica/european-ban-animal-testing-cosmetics-upheldhttp://crpc.kist.re.kr/common/attachfile/attachfileNumPdf.do?boardNo=00004944&boardInfoNo=0023&rowNo=1
Pre-clinical test
should be changed
Necessity of the research
Problems of in-vivo experiments
Draize Test
Replacement : Organ-on-a-Chip
Huh et al, 2012. Lab Chip.
• Limited experimental group
• Ethical problems
• Economical inefficiency
• Heterogeneous nature of cell
New drug development
Emerging Trends in Drug Screening
In vivo (animal)
screening
Phenomenological Low throughput
Disease relevance?
In vitro (biochemical)
screening
Target based High throughput
Disease relevance -‐ low
In vivo (immortalized cells)
screening
Target based High throughput Disease relevance?
In vivo (primary cells)
screening
Phenotypically based Low throughput
Disease relevance -‐ high
In vivo (ES and iPS cells)
screening
Phenotypically based High throughput
Disease relevance -‐ high
In vivo (3D tissue assemblies)
screening
Phenotypically based Throughput?
Disease relevance -‐ high
The history of Organ-on-a-chip
Neutrophil Chemotaxis
“Old” Tools Still Used in Biology
No Control Over Individual Cells, Cell-ECM and Cell-Cell Interactions
Custom “Apartments for Cells”and “Communities of Cells”
• Micrototal Analysis System (μTAS) • Genomic analysis• Protein analysis• High throughput screening• Cell Biology and Neuroscience
microfluidic gene sequencing LabChip µTAS (Caliper)
manipulation of fluids in small channels
Cell Sorter (Fluidigm)
Microfluidics
Multiscale Control of Cellular Microenvironments
2D Culture
Petri-dish culture
Life is in 3D
✓ Soluble gradients absent
✓ Forced apical-basal polarity
✓ Continuous layer of matrix
✓ Unconstrained spreading in x-y plane
✓ Adhesions restricted to x-y plane
✓ High stiffness
2D Culture
3D CultureChristopher S. Chen, Journal of cell science (2012)
Organ-on-a-chip
Organ-on-a-chip
Organ-on-a-Chip
Lung-on-a-Chip
Lung-on-a-Chip
Blood Vessel on a Chip:Toward Vascularized Micro-Tissue Engineered Constructs
Loading Gelsnad Cells in Spatially Controlled Manner
Vasculogenesis
Day 0
100 μⅿ
Vasculogenesis Microfluidic PlatformFibroblast-HUVEC-Fibroblast
in Fibrin-Collagen matrix Spontaneous network formation
Day 1
Day 3 Day 4
Day 2
100 µm
Day 1 Day 2
Day 3 Day 4
Vasculogenic Vessel Formation
100 um
xz plane
yz plane
*
* *
NucleiF-actin
CD31
xy plane
Lumen-Cross Section for Vasculogenic Vessels
Angiogenesis
Day 0
500 μⅿ
Day
1D
ay 2
Day
3D
ay 4
Aver
age
spro
ut le
ngth
(µm
) 700
525
350
175
0Day 1 Day 2 Day 3 Day 4
Vasc
ular
are
a co
vera
ge (%
) 80
60
40
20
0Day 1 Day 2 Day 3 Day 4
2 million cells/ml 3 million cells/ml
Vasculogenesis Angiogenesis
100 µm
Blood vessel formation
Vasculogenesis-derived network
Nuc
lei
F-a
ctin
C
D31
100 µm
Day 4
~ 88 % success rate (n = 36 chips)
Establishment of Perfusable Vessels
Microbeads flowing through the vascular network
NucleiICAM-1
Collagen IV
Vessel Characterization: Apical-Basal Polarity
FITC-dextran HUVECs
Extravascularfibrin matrix
Vessel Permeability (Fluorescent Dextran 70KD)
NucleusF-actin
Compatible with High Resolution Microscopy
Live-Cell Imaging of Tip Cell Dynamics
Engineering Functional, Perfusable 3D Microvascular Networks
Kim et al. Lab Chip, 2013 Selected as Top 10% paper, Research highlights
Blood Vessels On-A-Chip
24mm x 24mm coverslip
Organ-on-a Chip Research Groups
Korea University
3D in vitro disease model 3D tissue reconstruction
Translational research
Angiogenesis
Cancer metastasis
Seok Chung
SungkyunkwanUniversity
Sungsu Park
Pathogen detection chip
Cell elongation chip
Anticancer chip
Hongik University
3D in vitro gut model Multi organ on a chip
Jong Hwan Sung
Seoul National University
New Fabrication
Vasculature on a Chip Brain on a Chip
Cell Dynamics
Noo Li Jeon
Dan Huh
Gut-on-a-chip
Eye-on-a-chip
University of Pennsylvania
Lung-on-a-chip
Roger Kamm MIT
Biological machines / Microfluidics
Angiogenesis / Vasculogenesis
Cancer
Simulation and modeling
Shoji TakeuchiUniversity of Tokyo
3D tissue construction
Membrane protein chip
Neural interface
Companies : Organ-on-a-chip
Field of specification
Emulation human biology
Year Founded 2014
Total Funding $40Million
Recent Funding $28Million(March 28, 2016)
Headquarters Cambridge, Massachusetts
Size of corporation 25-50 employees
Website http://emulatebio.com
1. Emulate
https://emulatebio.com/insight/tedmed-2015/
Field of specification
Microfluidic,Organ on a chip
Year Founded 2013
Total Funding $8.4Million
Recent Funding $1.6Million(January 5, 2016)
Headquarters Leiden,Nederland
Size of corporation 35-50 employees
Website http://ww.mimetas.com
2. Mimetas
3D networks of iPSC-derived neurons and glia for high-throughput neurotoxicity screening, N.R. Wevers, K.J. Wilschut, R. van Vught, H.L. Lanz, S.J. Trietsch, J. Joore & P. Vulto
xxx
A human liver microphysiology platform for investigating physiology, drug safety, and disease models, Lawrence A. Vernetti, Nina Senutovitch, Robert Boltz
3. Nortis Bio
Field of specification
Microfluidic,Organ on a chip
Year Founded 2012
Total Funding $2.65Million
Recent Funding $0.41Million(March 19, 2015)
Headquarters Seattle,Washington
Size of corporation 30-40 employees
Website http://ww.nortisbio.com
xxx
A Micropatterned Hepatocyte Coculture Model for Assessment of Liver Toxicity Using High-Content Imaging Analysis. Assay Drug Dev Technol., Vol. 12 (1), p 16-27, (2014).
4. Hepregen
Field of specification
Liver,In-vitro testing
Year Founded 2007
Total Funding $3Million
Recent Funding $0.5Million(June 27, 2012)
Headquarters Medford,Massachusetts
Size of corporation 10-25 employees
Website http://www.hepregen.com
Summary
Summary1) Petri-dish culture 2) 2D patterned chip
4) Organ-on-a-chip 3) 3D Cell Spheroid
What is Organ-on-a-chip?
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