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Page 1: Organs-on-chips Market and Technology Landscape 2019yole-i-micronews-com.osu.eu-west-2.outscale.com/uploads/2019/10/… · Organs-on-chips Market and Technology Landscape 2019 | Sample

From Technologies to Markets

© 2019

From Technologies to Markets

© 2019

Organs-on-chips Market and Technology

Landscape 2019

Market and Technology Report

Sample

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Glossary and definitions p.2

Table of contents p.3

Report objectives p.5

Report scope p.6

Report methodology p.7

About the authors p.8

Companies cited in this report p.9

What we got right, What we got wrong p.10

Who should be interested by this report? p.11

Yole Group related reports p.12

Executive Summary p.13

Context p.59

o A problem to solve

o Other alternatives – which is best?

o Limitations of alternative methods (2D cell culture, 3D cell culture, organoids,

animal models, bioprinting)

o The big picture: a huge potential in a huge market

o Users and applications

o Drugs side effects and toxicity

o Main toxicity issues

o Future vision: personalized medicine

o What is an organ-on-chip?

o Is an organ-on-chip a real organ?

o Which organs can be emulated?

o What makes organ-on-chip technology relevant?

o How to ensure the models are relevant?

o Body on a chip: connecting several organs for a global understanding

o Organ-on-chip disease models

o Endpoints: what is measured?

o Summary

Market forecasts p.87

o Introduction

o How are OOC companies making revenue today?

o Business models

o Assumptions

o Market data and forecasts - comparison between the 2017 report and this report

o Market data and forecasts in value

o Market data and forecasts in units

o ASP evolution

o Conclusions

Market trends p.106

o Applications

o End-users have mitigated opinions about OOC

o How pharmaceutical companies are using OOC

o Relationship between OOC developers and pharmaceutical companies

o Application outside the pharmaceutical industry

o OOC won’t replace current workflows in the foreseeable future

o What’s the demand of the end-users?

o Expected impact on the industry

Organs-on-chips Market and Technology Landscape 2019 | Sample | www.yole.fr | ©2019

TABLE OF CONTENTS

Part 1/2

Imec’s organ-on-chip platform fuses imec’s high-density multi-electrode array (MEA)-chip with a microfluidic well plate, developed in collaboration with Micronit Microtechnologies, in which cells can be cultured, providing an environment that mimics human physiology

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TABLE OF CONTENTS

Part 2/2

o Too many OOC companies? The gap between established players and

newcomers

o Status of the market

o Public funding

o The role of regulators

o Challenges to address

o Who will use the OOC in the future?

o The OOC market paradox

o Where are we today?

o What do we expect?

o Conclusions

Market shares and supply chain p.134

o Organ-on-a-chip companies – geographical location

o Organ-on-chip ecosystem

o Market shares in value in 2018

o Evolution of the OOC companies’ revenue

o Fundraising table

o Manufacturing: who’s working with whom?

o Possible evolution and structuration of the market

o Could OOC companies purchase microfluidic fabs?

o Appearance of dedicated OOC CROs

o Value chain: cost of making a functioning organ-on-chip

o Conclusions

Technology trends p.146

o Who’s doing which organs matrix

o Most widespread organ models (ranking)

o End-users technical requirements

o Comparison of the different technologies

o Current limitations

o How many OOC are used?

o Two types of OOC: chips and plates

o Different types of OOC for different drug development stages

o From chip to plate

o Different types of OOC at different prices

o Single-organ vs. multi-organ models

o Towards a “human-on-a-chip”?

o Membrane-based devices

o Key aspects of organs-on-chips

o Different flow control modalities

o Where does microfluidics add value?

o Materials and manufacturing

o Materials change

o Material mix

o Emergence of new materials

o Towards an increased use of silicon in OOC?

o OOC instruments

o The importance of cells and biology

o Cell sources

o Disease models

o Conclusions

Company profiles p.189

Conclusions p.199

Yole Développement presentation p.202

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Marjorie Villien

As a Technology & Market Analyst, Medical & Industrial Imaging, Marjorie Villien, PhD., is member of the Photonics & Sensing activities group at YoleDéveloppement (Yole).

Marjorie contributes regularly to the development of imaging projects with a dedicated collection of market & technology reports as well as custom consulting services in the medical and industrial fields. She regularly meets with leading imaging companies to identify and understand technology issues, analyze market evolution and ensure the smart combination of technical innovation and industrial application.

After spending two years at Harvard and prior to her position at Yole, Marjorie served as a research scientist at INSERM and developed dedicated medical imaging expertise for the diagnosis and follow-up treatment of Alzheimer’s disease, stroke and brain cancers.

She presents to numerous international conferences throughout the year and has authored or co-authored 12 papers and 1 patent.

Marjorie Villien graduated from Grenoble INP (France) and holds a PhD. in physics & medical imaging.

Email: [email protected]

Sébastien Clerc

Sébastien Clerc is a Technology & Market Analyst in Microfluidics, Sensing & Actuating atYole Développement (Yole).

As part of the Photonics & Sensing team, Sébastien has authored a collection of market and technology reports dedicated to microfluidics and othermicro-devices for both market segments: medical (including diagnostics, pharmaceutical, biotechnology, drug delivery, medical devices) and industrial(including environment, agro-food).

At the same time, he is involved in custom projects such as strategic marketing, technology scouting and technology evaluation to help academic andindustrial players in their innovation processes. Thanks to his technology & market expertise, Sébastien has spoken in more than 20 industryconferences worldwide over the last 4 years.

Sébastien Clerc graduated from Grenoble Institute of Technology (Grenoble INP - Grenoble, France) with a Master’s degree in BiomedicalTechnologies. He then completed his academic studies with a Master’s degree in Innovation and Technology Management in the same institute.

Email: [email protected]

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ABOUT THE AUTHORS

Biographies & contacts

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4Design Biosciences, AIM Biotech, Allevi, Alnylam, AlveoliX, Amgen, Amore Pacific, Ananda Devices,Aspect Biosystems, Astellas, AstraZeneca, AxoSim, BASF, Barcelona Liver Bioservices, Beiersdorf,BeOnChip, Bioclinicum, Biogen, BiomimX, BI/OND, Bristol-Myers Squibb, Charles River, Charles StarkDraper Laboratory (Draper), CN Bio Innovations, CorSolutions, Covance, Creo Bioscience, Curiochips,DARPA, Denz Bio-Medical, Eli Lilly, Elveflow, Emulate, EpiSkin, ESA, Fluigent, Galapagos, GlaxoSmithKline(GSK), Harvard Medical School, Hesperos, Hurel Corporation, ICON plc, imec, InSphero, INTENZEProducts, Iontox, IQVIA, Javelin Biotech, Jiksak Bioengineering, Johnson & Johnson, Kirkstall, L’Oréal,Massachusetts Institute of Technology (MIT), Merck, MicroBrain Biotech, Microfluidic ChipShop,Micronit, Mimetas, MiniFAB, NASA, NCATS, NIH, Nortis, Organovo, Parexel, Parker Hannifin, Pfizer,Philip Morris, PimBio, Roche, Sanofi, Seattle Bioscience, Seres Therapeutics, Sigma-Aldrich, StemoniX,Stratec Consumables, Sun Bioscience, Syneos Health, Synvivo, Tara Biosystems, Tebu-bio, TissUse,Vanderbilt University, Vertex Pharmaceuticals, WYSS Institute, Xona Microfluidics, Yale University, andmore.

Organs-on-chips Market and Technology Landscape 2019 | Sample | www.yole.fr | ©2019

COMPANIES CITED IN THIS REPORT

200+ slides of market and technology analysis

Information gathered through direct discussions with players all along the supply chain

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This new Yole Développement report provides a complete analysis of the organ-on-chip market and technologyfields:

o New major trends and evolutions in the organ-on-chip industry market, feedback from end-users,evolution of business models, evolution of the hype

o Analysis of the requirements to boost the adoption of the technology and make organs-on-chips a successstory

o Updated market data and forecast up to 2024, in value and units, for organ-on-chip devices sales andservices

o Comparison with our 2017 report’s data and analysis

o Supply chain and ecosystem description and analysis, with projection future evolution

o Technical analysis: type of organ models, type of devices, importance of flow control, importance of cellsources, material mix, etc.

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REPORT OBJECTIVES

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We consider as organ-on-a-chip devices a combination of microtechnology and biology. All the deviceswe consider are micro-structured with injection molding or semiconductor-derived techniques.

Organs-on-chips result of the convergence of several areas of research:

• Microfluidics

• Microfabrication

• Tissue engineering

• Stem cell biology (providing easy access to non-malignant human cell lines and to patient-specific stemcells, enabling the creation of general human models and patient-specific models)

Other cell culture alternatives such as 3D cell culture, organoids and spheroids, are not part of thereport’s scope.

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REPORT SCOPE

Yours needs are

out of the report’s

scope?

Contact us for a custom:

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REPORT METHODOLOGY

Market

Volume (in Munits)

ASP (in $)

Revenue (in $M)

Yole’s market forecast model is based on the matching of several sources:

Information

Aggregation

Preexisting

information

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WHO SHOULD BE INTERESTED IN THIS REPORT?

Pharmaceutical, cosmetics, agro-food, chemistry, consumer goods and other companies, including CROs:

o To understand what are organ-on-chip technologies

o To understand what is the state of the art and which solutions could bring operational benefits versus other technologies

o To identify the different organs-on-chips players, types of organs emulated and specificities of the different models

o To understand behavior evolution

R&D players:

o To understand new challenges linked to organs-on-chips

o To address the right market with the right technology

Financial & strategic investors:

o To understand the potential for organ-on-chips

o To know the latest moves within the industry

o To get a list and description of OOC players

o To understand which are the sweet spots and what are the end-users pushing for

Organ-on-chip developerso To monitor and benchmark potential

competitorso To understand how to address the

right market with the right technologyo To understand the end-users

requirements and adapt their offer

Microfluidic foundries and device makers:

o To understand technical requirementso To identify business opportunities and

prospects

Healthcare and governmental organizations:

o To evaluate benefits of OOC technologies

o To identify relevant companies

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CONTEXT

A problem to solve (1/2)

5k – 10k

compounds

100 – 500

compounds

50 – 250

compounds 1 compound

CommercializationDrug discovery Preclinical trials Clinical trials ValidationPreclinical research

3 – 5

compounds

Total cost: $2.6 billion in average

5+ years 10+ years 12+ years

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CONTEXT

A problem to solve (2/2)

In-development drugs have a very high failure rate in clinical trials.

In many cases, drugs have different effects on 2D cell cultures and

animals vs. humans: around 90% of drugs validated on animals

during pre-clinical trials fail during human clinical trials.

Thus there is a need for solutions that enable better predictive, physiologically-relevant in-

vitro drug testing. This could save hundreds of millions of dollars in development costs and

avoid major timeline delays for a single drug.

In many cases, cell models, 3D culture models, and animal models do not adequately

represent human biology. Consequently, a large part of the total pharma R&D budget is spent

on drugs that ultimately fail in human clinical trials.

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Organs-on-chips result of the convergence of several areas of research:

• Microfluidics

• Microfabrication

• Tissue engineering

• Stem cell biology (providing easy access to non-malignant human cell lines and to patient-

specific stem cells, enabling the creation of general human models and patient-specific models)

CONTEXT

What is an organ on a chip? (1/2)

It is a micro-engineered device lined with living human cells, which model and reconstitute the physiological and mechanical functions of a human organ.

Organs-on-chips Market and Technology Landscape 2019 | Sample | www.yole.fr | ©2019

A combination of microtechnology…

… and biology

Fraunhaufer IGB’s retina-on-a-chip

Lung-on-a-chip model developed at the WYSS Institute

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CONTEXT

What is an organ on a chip? (2/2)

• It is a micro-engineered device lined with living human cells, which model and reconstitute the physiological and mechanicalfunctions of a human organ

• Microfabrication techniques coming from the semiconductor industry allows to control the features of the bioengineered organat a microscale or below, which is similar to the cell scale at the organ level.

• Current product applications:

• Understanding biological mechanisms for novel drug targets

• Providing insight into disease processes

• Predicting the efficacy and safety of new drug candidates

• Screening using much lower drug amounts

• Explore species differences and unexpected clinical findings

• Implementation of 3Rs – reduction, refinement and replacement – of animal testing

• Toxicity tests

• Development of clinical diagnostics

• Personalized health applications

• Organs on chips can be used in a variety of domains:

• Pharmaceutical companies: drug development, disease modeling, toxicity test, personalized medicine…

• Cosmetics: toxicity screening…

• Environment health: chemicals, air, food…

Mimetas kidney on a chip

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Bio-technology

Academia

Chemicals and

environmentPharmaceutical

AgricultureCosmetics

CONTEXT

Markets and applications

The applications of organs-on-chip are ranging from toxicity test to drug discovery.

Drug discovery

Personalized medicine

Safety/ toxicity test

Drug efficacy

Disease modeling

Markets Applications

Organs-on-chips Market and Technology Landscape 2019 | Sample | www.yole.fr | ©2019

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CONTEXT

Drug side effects and toxicity

• Though physicians prescribe drugs to prevent or treat disease, these drugs can be harmful to certain patients because ofinappropriate use (high dose or drug-drug interaction), non-selective action, age of the patient or genetic predisposition.

• Indeed, all drugs may have both primary intended effects and unintended secondary side effects which can be undesirable.

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CONTEXT

Main toxicity issues

The liver and kidney are particularly susceptible to

organ toxicity, as they are in charge of toxin

filtration and toxin metabolic breakdown.

The use of a drug, particularly when repeated, can lead to an accumulation of harmful compounds in tissues or organs from

the metabolism of this drug. This accumulation of toxic compounds can lead to organ damage or even organ failure and death.

The heart is also one of the organs the most

commonly affected by drug toxicity (especially with

chemotherapy drugs).

Moreover, many other organs can be affected by drug

toxicity, either directly or via drug metabolites (e.g.

generated by the liver following the intake of the drug).

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CONTEXT

Future vision: personalized medicine (1/2)

Individually tailored Organs-on-Chips with a patient’s own cells, to allow biology to be predicted on a person-by-person basis.

Organs-on-chips Market and Technology Landscape 2019 | Sample | www.yole.fr | ©2019

Now

Personalized

organs on chip

containing

one’s personal

living cells

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CONTEXT

Future vision: personalized medicine (2/2)

Everyone will benefit from personalized organs on chips.

Organs-on-chips Market and Technology Landscape 2019 | Sample | www.yole.fr | ©2019

• For pharmaceutical companies, personalized testing means that drugs that so far failed to show efficacy forthe global patient population could be marketed for the specific pool of patients where they do work. Thiscould be a significant new source of revenues for the pharmaceutical industry.

• For patients, personalized testing means to pre-select the medications that work for them (depending on age,gender, genetic predispositions…), resulting altogether in more effective and cost-effective therapies.

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MARKET DATA AND FORECASTS

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MARKET TRENDS (1/2)

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MARKET SHARES AND SUPPLY CHAIN (1/2)

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TECHNOLOGY TRENDS

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TECHNOLOGY TRENDS

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COMPANY PROFILES

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Contact our

Sales Team

for more

information

Liquid Biopsy: From Isolation to Downstream Applications 2018

Next-Generation Sequencing & DNA Synthesis 2019

Status of the Microfluidics Industry 2019

Point-of-Need Testing: Application of Microfluidic

Technologies 2018

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Yole Développement

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Organs-on-chips (OOC) has the potential to enable better predictive, physiologically-relevant in-vitro drug testing. This could save hundreds of millions of dollars in development costs, reduce drug development time, and avoid failures due to lack of predictiveness from alternative models like 2D cell cultures and animals. Burgeoned by these promises, the OOC market increased 4-fold from 2016 - 2018 (from $7.5M to $29.6M), and will grow at a CAGR2018-2024 of 28,6%.

Many new players are entering this market with new organ models, and most players that were present two years ago have made noticeable progress. Top players like Mimetas and TissUse now have recurring sales and a consistent revenue stream, and many players are leveraging their OOC devices to provide testing services to

their partners in the pharmaceutical, cosmetics, and consumer goods industries - for testing the efficacy and safety of new drugs and products. Evolving regulations in certain countries and industries have spurred a push towards the use of in-vitro models instead of animal models. In the pharmaceutical industry, the real potential of the technology conclusively lies in the promise it holds for personalized medicine. Indeed, it could be possible to create individually-tailored OOC with a patient’s own cells, allowing a substance’s effects to be predicted on an individual basis. In this report, Yole Développement’s (Yole) analysts explain how reaching such milestones could create a real inflexion point, causing the OOC market to skyrocket. However, this is a long-term vision that will not materialize over the next five years.

ORGANS-ON-CHIPS MARKET AND TECHNOLOGYLANDSCAPE 2019Market & Technology Report - October 2019

Market growth is pushing changes in materials and technologies.

WHAT’S NEW• What has happened in the last two years • What we got right, what we got wrong • Updated and refined market forecasts and assumptions • Market-share evolution • Identification of new entrants • Analysis of the role of various players, including contract research organizations• Evolution of the materials mix, and future projections

KEY FEATURES• Major trends and evolutions in the organs-on-chips industry, feedback from end-users, evolution of business models, evolution of “the hype” • Analysis of the requirements to boost the technology’s adoption and make organs-on-chips a success story • Updated market data and forecast up to 2024, in value and units for organ- on-chip device sales and services • Comparison with Yole Développement 2017 report’s data and analysis • Supply chain and ecosystem description and analysis, with projections for future evolution • Technical analysis: type of organ models, device types, importance of flow control, importance of cell sources, materials mix, etc.

TOO MANY EXPECTATIONS, TOO MUCH HYPE?

$12.5$M (42%)

$29.6M2018

2024Revenue from sales of organ-on-chips devices

Revenue from testing services

*CAGR2018-2024 = +28.6%

$60.8$M(45%)

$133.9M

$17$M (58%) $73.0$M

(55%)

*CAGR: Compound Annual Growth Rate

Since OOC holds great promise, the associated expectations are extremely high. Personalized medicine, fully replacing current in-vitro and in-vivo models, for disease modelling? We have entered a phase where end-users don’t expect such results yet - but they do expect reproducibility and automation. Though OOC companies claim to have positive feedback from end-users overall, the comments from end-users are more restrained. The problem is that most OOC models are still “proof-of-concept”, whereas end-users prefer industry-grade models with validated processes

and outcomes. In this report, Yole’s analysts explain the reasons for such negative feedback, and what the end-users’ expectations are.

OOC technology is intriguing, but it is struggling to generate a consensus. Consequently, OOC companies strain to find the ideal business model: most end up adopting a hybrid business model combining product sales and services, because even though different users have different demands, OOC firms cannot say “no”. Ultimately though, each company must find the right balance inspired by its strengths, instead of trying to please every customer.

(Yole Développement, October 2019)

A RAPID PACE FOR A HIGH-POTENTIAL MARKET

Organs-on-chips market: 2018 - 2024 forecast

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ORGANS-ON-CHIPS IS A MULTIDISCIPLINARY FIELD, AND VARIOUS PARAMETERS WILL SHAPE TOMORROW’S TECHNOLOGY

Organs-on-chips user chain: Midterm future prediction*

1

ORGAN-ON-CHIPS USER CHAIN: MID-TERM FUTURE PREDICTION

Organs-on-chips companies

Contract research organizations

Pharmaceutical companies

Provide organs-on-chips devices and models

Offer testing services on organs-on-chips

Non-exhaustive list of companies

(Yole Développement, October 2019)

REPORT OBJECTIVES• Detail new major trends and evolutions in the OOC industry • Evaluate end-users’ feedback, and the impact it has on the evolution of business models, hype, etc. • Discern end-users’ key requirements for widespread adoption of the technology, and where the gap is today • Provide updated market data and forecasts up to 2024, in value and units for OOC device sales and services, and a comparison with our 2017 report’s data and analysis • Describe the supply chain and ecosystem, and discuss future evolutions • Deliver a comprehensive technical analysis: type of organ models, device types, importance of flow control, importance of cell sources, evolution of the materials mix, etc.

The OOC industry’s maturation could signal the beginning of contract research organizations’ (CROs) involvement. Today, CROs seem minimally involved in the OOC field, and are waiting for more evidence of the technology’s potential. However, CROs are usually the privileged subcontractors of the pharmaceutical, cosmetics, and consumer goods industries for safety and efficacy testing - and in a midterm future, they will certainly be the primary users of OOC in order to perform testing services for the pharma industry. Also, they will work closely with OOC companies to learn how to best use their models. That said, it’s too early to speculate, and additional data must be generated to prove OOC’s relevance over the gold standards CROs have used for decades.

ORGANS-ON-CHIPS MARKET AND TECHNOLOGY LANDSCAPE 2019

*Non exhaustive list of companies

2024

13 %

21 %

56 %

10 %PDMSPolymerGlassSilicon

2016

18 %

15 %

67 %

2018

20 %

54 %

25 %

36 kUnits

146kUnits

790 kUnits

*CAGR: Compound Annual Growth Rate

Volume CAGR*2018-2024= + 32,4%

(Yole Développement, October 2019)

Evolution and forecast of the organs-on-chips material mix in volume

*Non exhaustive list of companies

Organs-on-chips can take various shapes and appearances, depending on their purpose. The drug development process is long and complex, and the needs are not the same at the early drug-screening stages as they are in the late preclinical trial stages. Thus, we see some players specializing in plate formats for automation and high throughput, while others prefer developing single independent chips.

Some players develop key solutions based on single organ models, while others propose multi-organ models to assess metabolic interactions between organs. Every technology is different and has specific application domains.

On the materials side, important changes are happening. Two years ago, Yole’s analysts were concerned about the ability of OOC companies to switch from PDMS devices in order to scale-up production. Today, it appears that most companies have successfully managed this transition, or at least engaged with the right partners early enough to avoid the problems young companies usually face at this stage. At the moment, polymer is the preferred material, but some companies use glass. The next step could be the integration of more silicon pieces: indeed, sensing directly at the cell level is a necessity, but right now only a few companies are moving in this direction. This is why silicon is not commonly used in OOC. Yole’s analysts expect this to change by 2024, and in this report they detail the evolution of the materials mix, along with various other technical aspects such as the added-value of flow control and vascularization of organs, the emergence of new materials combining the preferred properties of several existing ones, the importance of cell sources, and more.

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COMPANIES CITED IN THE REPORT (non exhaustive list)

4Design Biosciences, AIM Biotech, Allevi, Alnylam, AlveoliX, Amgen, Amore Pacific, Ananda Devices, Aspect Biosystems, Astellas, AstraZeneca, AxoSim, BASF, Barcelona Liver Bioservices, Beiersdorf, BeOnChip, Bioclinicum, Biogen, BiomimX, BI/OND, Bristol-Myers Squibb, Charles River, Charles Stark Draper Laboratory (Draper), CN Bio Innovations, CorSolutions, Covance, Creo Bioscience, Curiochips, DARPA, Denz Bio-Medical, Eli Lilly, Elveflow, Emulate, EpiSkin, ESA, Fluigent, Galapagos, GlaxoSmithKline (GSK), Harvard Medical School, Hesperos, Hurel Corporation, ICON plc, imec, InSphero, INTENZE Products, Iontox, IQVIA, Javelin Biotech, Jiksak Bioengineering, Johnson & Johnson, Kirkstall, L’Oréal, Massachusetts Institute of Technology (MIT), Merck, MicroBrain Biotech, Microfluidic ChipShop, Micronit, Mimetas, MiniFAB, NASA, NCATS, NIH, Nortis, Organovo, Parexel, Parker Hannifin, Pfizer, Philip Morris, PimBio, Roche, Sanofi, Seattle Bioscience, Seres Therapeutics, Sigma-Aldrich, StemoniX, Stratec Consumables, Sun Bioscience, Syneos Health, Synvivo, Tara Biosystems, Tebu-bio, TissUse, Vanderbilt University, Vertex Pharmaceuticals, WYSS Institute, Xona Microfluidics, Yale University, and more.

Glossary and definitions 2Table of contents 3Report objectives 5 Report scope 6

Report methodology 7

About the authors 8

Companies cited in this report 9What we got right, what we got wrong 10Who should be interested in this report? 11 Yole Group’s related reports 12Executive summary 13Context 51

> A problem to solve > Limitations of alternative methods (2D cell culture, 3D cell culture, organoids, animal models, bioprinting) > The big picture: huge potential in a huge market > Future vision: personalized medicine > What is an organ-on-chip? > What makes OOC technology important? > Body-on-a-chip: connecting several organs for a comprehensive understanding > Organ-on-chip disease models

Market forecasts 79> How are OOC companies generating revenue today? > Business models > Assumptions > Market data and forecasts: comparison between the 2017 report and this report > Market data and forecasts, in value and units > ASP evolution

Market trends 96> Relationship between OOC developers and pharmaceutical companies

> Applications beyond the pharmaceutical industry > OOC won’t replace current workflows in the foreseeable future > What’s the demand from end-users? > Market status > The OOC market paradox > Where are we today? > What do we expect?

Market share and supply chain 123> Organ-on-chip companies - geographic location> Organ-on-chip ecosystem> 2018 market share, in value > Evolution of OOC companies’ revenue> Fundraising table> Manufacturing: who’s working with whom?> Possible market evolution and structuration > Appearance of dedicated OOC CROs> Value chain: cost of making a functioning organ-on-chip

Technology trends 137> Who’s doing which organs: matrix> Most widespread organ models (ranking)> Current limitations> Two types of OOC: chips and plates> Different OOC types for different drug development stages> From chip to plate> Different OOC types at different prices> Different flow-control modalities> Where does microfluidics add value?> Materials and manufacturing> Emergence of new materials> Towards an increased use of silicon in OOC?

Company profiles 176Conclusions 186Yole Développement presentation 189

TABLE OF CONTENTS (complete content on i-Micronews.com)

• Status of the Microfluidics Industry 2019 • Point-of-Need Testing: Application of Microfluidic Technologies 2018• Liquid Biopsy: From Isolation to Downstream Applications 2018

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AUTHORSSébastien Clerc works as a Technology & Market Analyst, Microfluidics, Sensing & Actuating at Yole Développement (Yole). As part of the Photonics & Sensing activities, Sébastien has authored a collection of market and technology reports dedicated to microfluidics and other micro-devices for both market segments: medical (including diagnostics, pharmaceutical, biotechnology, drug delivery, medical devices) and industrial (including environment, agro-food). In parallel, he is daily involved in custom projects such as strategic marketing, technology scouting and technology evaluation to help academic and industrial players in their innovation processes. Thanks to his technology & market expertise, Sébastien has spoken in more than 20 industry conferences worldwide over the last 4 years. Sébastien Clerc graduated from Grenoble Institute of Technology (Grenoble INP - Grenoble, France) with a Master’s degree in Biomedical Technologies. He then completed his cursus with a Master’s degree in Innovation and Technology Management in the same institute.

Marjorie Villien, PhD. is Technology & Market Analyst, Medical & Industrial Imaging at Yole Développement (Yole).As a member of the Photonics & Sensing activities, Marjorie contributes regularly to the development of imaging projects with a dedicated collection of market & technology reports as well as custom consulting services in the medical and industrial fields. She regularly meets with leading imaging companies to understand technology issues, analyze market evolution and ensure the smart combination of technical innovation and industrial application.Marjorie Villien graduated from Grenoble INP (France) and holds a PhD. in physics & medical imaging.

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Founded in 1998, Yole Développement (Yole) has grown to become a group of companies providing marketing, technology and strategy consulting, media and corporate finance services, reverse engineering and reverse costing services and well as IP and patent analysis. With a strong focus on emerging applications using silicon and/or micro manufacturing, the Yole group of companies has expanded to include more than 120 collaborators worldwide covering MEMS and image sensors, Compound semiconductors, RF Electronics, Solid-state lighting, Displays, Software, Optoelectronics, Microfluidics & Medical, Advanced Packaging, Manufacturing, Power Electronics, Batteries & Energy Management and Memory.The “More than Moore” market research, technology and strategy consulting company Yole Développement, along with its partners System Plus Consulting, PISEO, KnowMade and Blumorpho, supports industrial companies, investors and R&D organizations worldwide to help them understand markets and follow technology trends to grow their business.

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6 COMPANIES TO SERVE YOUR BUSINESS

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ANALYSIS SERVICES - CONTENT COMPARISON

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o Over the course of more than 20 years, Yole Développement has grown to become a group of companies. Together with System Plus Consulting and KnowMade, we now

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OUR 2019 REPORTS COLLECTION (1/4)

18 fields of excellence combined with six markets to provide a complete picture of your industry landscape

Market –Technology – Strategy – by Yole DéveloppementYole Développement (Yole) offers market reports including quantitative market forecasts,

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components from System Plus Consulting. More reports are however available, and over

60 reports will be released in 2019.The complete list is available at www.systemplus.fr.

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OUR 2019 REPORTS COLLECTION (1/5)18 fields of excellence combined with six markets to provide a complete picture of your industry landscape

MEMS & SENSORS

o MARKET AND TECHNOLOGY REPORT

• Status of the MEMS Industry 2019 - Update

• Status of the Audio Industry 2019 - New

• Uncooled Infrared Imagers and Detectors 2019 – Update

• Consumer Biometrics:Technologies and Market Trends 2018

• MEMS Pressure Sensor Market and Technologies 2018

• Gas & Particle Sensors 2018

o STRUCTURE, PROCESS & COST REPORT

• MEMS & Sensors Comparison 2019

• MEMS Pressure Sensor Comparison 2018

• Particle Sensors Comparison 2019

• Miniaturized Gas Sensors Comparison 2018

o PATENT REPORT

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• Miniaturized Gas Sensors 2019 - New

PHOTONIC AND OPTOELECTRONICS

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• Silicon Photonics and Photonic Integrated Circuits 2019

• LiDARs for Automotive and Industrial Applications 2019 - Update

o PATENT REPORT

• Silicon Photonics for Data Centers: Optical Transceiver 2019 - New

• LiDAR for Automotive 2018

RF DEVICES AND TECHNOLOGIES

o MARKET ANDTECHNOLOGY REPORT

• RF GaN Market: Applications, Players, Technology,

and Substrates 2019 - Update

• 5G’s Impact on RF Front-End Module and Connectivity

for Cell Phones 2019 – Update

• 5G Impact on Telecom Infrastructure 2019 - New

• Radar and Wireless for Automotive: Market and Technology

Trends 2019 - Update

• Passive & Active Antenna Systems for Telecom

Infrastructure 2019 - New

• RF Standards and Technologies for Connected Objects 2018

o STRUCTURE, PROCESS & COST REPORT

• RF Front-End Module Comparison 2019 - Update

• Automotive Radar RF Chipset Comparison 2018

o PATENT REPORT

• Antenna for 5G Wireless Communications 2019 - New

• RF Front End Modules for Cellphones 2018

• RF Filter for 5G Wireless Communications: Materials and Technologies 2019

• RF GaN 2019 – Patent Landscape Analysis

Update : 2018 version still available About Yole Développement | www.yole.fr | ©2019

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OUR 2019 REPORTS COLLECTION (2/5)18 fields of excellence combined with six markets to provide a complete picture of your industry landscape

IMAGING

o MARKET AND TECHNOLOGY REPORT

• Status of the CIS Industry 2019: Technology

and Foundry Business - Update

• Imaging for Automotive 2019 - Update

• Neuromorphic Technologies for Sensing 2019 - Update

• Status of the CCM and WLO Industry 2019 – Update

• 3D Imaging & Sensing 2018

• MachineVision for Industry and Automation 2018

• Sensors for Robotic Vehicles 2018

o STRUCTURE, PROCESS & COST REPORT

• Compact Camera Modules Comparison 2019

• CMOS Image Sensors Comparison 2019

o PATENT REPORT

• Facial & Gesture Recognition Technlogies in Mobile Devices 2019 - New

• Apple iPhone X Proximity Sensor & Flood Illuminator 2018

MEDICAL IMAGING AND BIOPHOTONICS

o MARKET ANDTECHNOLOGY REPORT

• X-Ray Detectors for Medical, Industrial

and Security Applications 2019- New

• Microscopy Life Science Cameras: Market and Technology Analysis 2019

• Ultrasound technologies for Medical, Industrial

and Consumer Applications 2018

o PATENT REPORT

• Optical Coherence Tomography Medical Imaging 2018

MICROFLUIDICS

o MARKET ANDTECHNOLOGY REPORT

• Status of the Microfluidics Industry 2019 - Update

• Next Generation Sequencing & DNA Synthesis - Technology,

Consumables Manufacturing and Market Trends 2019 - New

• Organs-on-chips Market and Technology Landscape 2019 - Update

• Point-of-Need Testing Application of Microfluidic Technologies 2018

• Liquid Biopsy: from Isolation to Downstream Applications 2018

• Chinese Microfluidics Industry 2018

o PATENT REPORT

• Microfluidic Manufacturing Technologies 2019 – New

• Nanopore Sequencing 2019 - New

INKJET AND ACCURATE DISPENSING

o MARKET ANDTECHNOLOGY REPORT

• Inkjet Printheads - Dispensing Technologies

& Market Landscape 2019 - Update

• Emerging Printing Technologies

for Microsystem Manufacturing 2019 - New

• Piezoelectric Devices from Bulk to Thin Film 2019 - New

• Inkjet Functional and Additive Manufacturing for Electronics 2018

o STRUCTURE, PROCESS & COST REPORT

• Piezoelectric Materials from Bulk to Thin Film Comparison 2019

Update : 2018 version still available About Yole Développement | www.yole.fr | ©2019

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OUR 2019 REPORTS COLLECTION (3/5)18 fields of excellence combined with six markets to provide a complete picture of your industry landscape

BIOMEMS & MEDICAL MICROSYSTEMS

o MARKET ANDTECHNOLOGY REPORT

• Medical Wearables: Market & Technology Analysis 2019 - New

• Neurotechnologies and Brain Computer Interface 2018

• BioMEMS & Non-Invasive Sensors: Microsystems for Life Sciences

& Healthcare 2018

o PATENT REPORT

• 3D Cell Printing 2019 - New

• Circulating Tumor Cells Isolation 2019 - New

SOFTWARE AND COMPUTING

o MARKET ANDTECHNOLOGY REPORT

• Artificial Intelligence Computing For Automotive 2019 - New

• Hardware and Software for Artificial Intelligence (AI)

in Consumer Applications 2019 - Update

• Image Signal Processor and Vision Processor Market

and Technology Trends 2019

• xPU (Processing Units) for Cryptocurrency, Blockchain, HPC

and Gaming 2019 – New

• Artificial Intelligence for Medical Imaging 2019 - New

o PATENT REPORT

• Artificial Intelligence for Medical Diagnostics - New

MEMORY

o MARKET AND TECHNOLOGY REPORT

• Status of the Memory Industry 2019 - New

• MRAM Technology and Business 2019 - New

• Emerging NonVolatile Memory 2018

o STRUCTURE, PROCESS & COST REPORT

• Memory Comparison 2019

o PATENT REPORT

• Magnetoresistive Random-Access Memory (MRAM) 2019 - New

• 3D Non-Volatile Memory 2018

ADVANCED PACKAGING

o MARKET ANDTECHNOLOGY REPORT

• Fan Out Packaging Technologies and Market Trends 2019 - Update

• 3D TSV Integration and Monolithic Business Update 2019 - Update

• Advanced RF SiP for Cellphones 2019 - Update

• Status of the Advanced Packaging Industry 2019 - Update

• Status of the Advanced Substrates 2019 - Update

• Panel Level Packaging Trends 2019 - Update

• Automotive Packaging Market & Technology Trends 2019 - New

• Trends in Automotive Packaging 2018

• Thin-Film Integrated Passive Devices 2018

o STRUCTURE, PROCESS & COST REPORT

• Advanced RF SiP for Cellphones Comparison 2019

Update : 2018 version still available About Yole Développement | www.yole.fr | ©2019

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OUR 2019 REPORTS COLLECTION (4/5)18 fields of excellence combined with six markets to provide a complete picture of your industry landscape

SEMICONDUCTOR MANUFACTURING

o MARKET ANDTECHNOLOGY REPORT

• Nano-Imprint Technology Trends for Semiconductor

Applications 2019 - New

• Equipment and Materials for Fan Out Packaging 2019 - Update

• Equipment for More than Moore: Thin Film Deposition

& Etching 2019 - New

• Wafer Starts for More Than Moore Applications 2018

• Polymeric Materials at Wafer-Level

for Advanced Packaging 2018

• Bonding and Lithography Equipment Market

for More than Moore Devices 2018

o STRUCTURE, PROCESS & COST REPORT

• Wafer Bonding Comparison 2018

o PATENT REPORT

• Hybrid Bonding for 3D Stack 2019 – New

BIOTECHNOLOGIES

o MARKET AND TECHNOLOGY REPORT

• CRISPR-Cas9 Technology: From Lab to Industries 2018

o PATENT REPORT

• Personalized Medicine 2019 – New

SOLID STATE LIGHTING

o MARKET ANDTECHNOLOGY REPORT

• Status of the Solid State Light Source Industry 2019 - New

• Edge Emitting Lasers (EELS) 2019 - New

• Light Shaping Technologies 2019 - New

• Automotive Advanced Front Lighting Systems 2019 - New

• VCSELs – Market and Technology Trends 2019 - Update

• IR LEDs and Laser Diodes – Technology, Applications,

and Industry Trends 2018

• Automotive Lighting 2018: Technology, Industry and Market Trends

• UV LEDs - Technology, Manufacturing and Application Trends 2018

• LiFi: Technology, Industry and Market Trends 2018

o STRUCTURE, PROCESS & COST REPORT

• VCSEL Comparison 2019

o PATENT REPORT

• VCSELs 2018

DISPLAY

o MARKET ANDTECHNOLOGY REPORT

• Next Generation 3D Displays 2019 - New

• Next Generation Human Machine Interaction (HMI)in Displays 2019 - New

• Micro-and Mini-LED Displays 2019 - Update

• Next Generation TV Panels: New Technologies, Features and

Market Impact 2019

• Displays & Optical Vision Systems for VR, AR & MR 2018

o PATENT REPORT

• MicroLED Displays : Intellectual Property Landscape 2018Update : 2018 version still available About Yole Développement | www.yole.fr | ©2019

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OUR 2019 REPORTS COLLECTION (5/5)18 fields of excellence combined with six markets to provide a complete picture of your industry landscape

POWER ELECTRONICS

o MARKET ANDTECHNOLOGY REPORT

• Power SiC: Materials, Devices and Applications 2019 - Update

• Power Electronics for EV/HEV and e-mobility:

Market, Innovations and Trends 2019 - Update

• Status of the Power Electronics Industry 2019 - Update

• Discrete Power Packaging : Material Market

and Technology Trends 2019 - New

• Status of the Power ICs Industry 2019 - Update

• Status of the Passive Components for the Power Electronics

Industry 2019 - Update

• Status of the Inverter Industry 2019 - Update

• Status of the Power Module Packaging Industry 2019 - Update

• Wireless Charging Market Expectations

and Technology Trends 2018

• Power GaN 2018: Epitaxy, Devices, Applications

and Technology Trends

o STRUCTURE, PROCESS & COST REPORT

• Automotive Power Module Packaging Comparison 2018

• GaN-on-Silicon Transistor Comparison 2019

• SiC Transistor Comparison 2019

o PATENT REPORT

• Power SiC : Materials, Devices and Modules 2019 - New

• Power GaN : Materials, Devices and Modules 2019 – Update

BATTERY & ENERGY MANAGEMENT

o MARKET ANDTECHNOLOGY REPORT

• Status of the Rechargeable Li-ion Battery Industry 2019 - New

• Li-ion Battery Packs for Automotive and Stationary Storage

Applications 2019 - Update

o PATENT REPORT

• Battery Energy Density Increase: Materials

and Emerging Technologies 2019 - New

• Solid-State Batteries 2019 - New

• Status of the Battery Patents 2018

COMPOUND SEMI.

o MARKET ANDTECHNOLOGY REPORT

• Emerging Semiconductor Substrates:

Market & Technology Trends 2019- New

• Status of the Compound Semiconductor Industry 2019 - New

• InP Materials, Devices and Applications 2019 - New

• GaAs Wafer and Epiwafer Market: RF, Photonics,

LED and PV Applications 2018

o PATENT REPORT

• GaN-on-Silicon Substrate: Materials, Devices

and Applications 2019 - Update

Update : 2018 version still available About Yole Développement | www.yole.fr | ©2019

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OUR 2019 MONITORS COLLECTION (1/2)

Get the most updated overview of your market to monitor your strategy

Yole Développement, System Plus Consulting and KnowMade, all part of the Yole Group of Companies, are launching a collection of 10 monitors in 2019. The monitors aim to

provide updated market, technology and patent data as well dedicated quarterly analyses of the evolution in your industry over the previous 12 months. Furthermore, you can

benefit from direct access to the analyst for an on-demand Q&A and discussion session regarding trend analyses, forecasts and breaking news.

Topics covered will be compact camera modules (CCMs), advanced packaging, compound semiconductors, microfluidics, batteries, RF and memory.

MARKET MONITOR byYole Développement

A FULL PACKAGE:The monitors will provide the evolution of the market in units, wafer area and revenues.They will also offer insights into what is driving the business and a close look at what ishappening will also be covered in it.

The following deliverables will be included in the monitors:

• An Excel database with all historical and forecast data

• A PDF slide deck with graphs and comments/analyses covering the expected

evolutions

o ADVANCED PACKAGING – NEWThis monitor will provide the evolution of the advanced packaging platforms. It willcover Fan-Out Wafer Level Packaging (WLP), Fan-Out Panel Level Packaging (PLP),Wafer-Level Chip Scale Packaging (WLCSP), Flip Chip packaging platforms, and 2.5Dand 3D Through Silicon Via (TSV) integration. Frequency: Quarterly, starting from Q32019

o COMPOUND SEMI. – NEWThis monitor will describe how the compound semiconductor industry is evolving. Itwill offer a close look at GaAs, InP, SiC, GaN and other compounds of interestproviding wafer volumes, revenues, application breakdowns and momentum.Frequency: Quarterly, starting from Q3 2019

o CAMERA MODULE – NEWThis monitor will provide the evolution of the imaging industry, with a close look atimage sensor, camera module, lens and VCM. Volumes, revenues and momentum ofcompanies like Sony, Samsung, Omnivision and OnSemi will thus be analysed.Frequency: Quarterly, starting from Q3 2019

o MEMORY – UPDATEFor the memory industry you can have access to a quaterly monitor, as well as anadditional service, a monthly pricing. Both services can be bought seprately:

• DRAM Service: Including a quarterly monitor and monthly pricing.

• NAND Service: Including a quarterly monitor and monthly pricing.

REVERSETECHNOLOGY MONITOR by System Plus Consulting

o SMARTPHONES – NEWTo stay updated on the latest components, packaging and silicon chip choices of the smartphone makers, System Plus Consulting has created its first Smartphone ReverseTechnology monitor. This year, get access to the packaging and silicon content database of at least 20 different flagship smartphones – more than five per quarter. Starting at thebeginning of 2019, the monitor will include an Excel database report for each phone and a quarterly comparison.

About Yole Développement | www.yole.fr | ©2019

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OUR 2019 MONITORS COLLECTION (2/2)

Get the most updated overview of your market to monitor your strategy

PATENT MONITOR by KnowMade

A FULL PACKAGE:Starting at the beginning of the year, the KnowMade monitors include the following deliverables:

• An Excel file including the monthly IP database of:

• New patent applications

• Newly granted patents

• Expired or abandoned patents

• Transfer of IP rights through re-assignment and licensing

• Patent litigation and opposition

• Quarterly report including a PDF slide deck with the key facts & figures of thequarter: IP trends over the three last months, with a close look to key IP players andkey patented technologies.

o GaN for Power & RF ElectronicsWafers and epiwafers, GaN-on-SiC, silicon, sapphire or diamond, semiconductordevices such as transistors, and diodes, devices and applications including converters,rectifiers, switches, amplifiers, filters, and Monolothic Microwave Integrated Circuits(MMICs), packaging, modules and systems.

o GaN for Optoelectronics & PhotonicsWafers and epiwafers, GaN-on-sapphire, SiC or silicon; semiconductor devices suchas LEDs and lasers; and applications including lighting, display, visible communication,photonics, packaging, modules and systems.

o Li-ion BatteriesAnodes made of lithium metal, silicon, and lithium titanate (LTO); cathodes made ofLithium Iron Phosphate (LFP), Nickel-Manganese-Cobalt (NMC), Lithium NickelCobalt Aluminium Oxide (NCA), Lithium Nickel Metal Dioxide (LiNiMO2), LithiumMetal Phosphate (LiMPO4), and Lithium Metal Tetroxide (LiMO4); electrolytesincluding liquid, polymer/gel, and solid inorganics; ceramic and other separators;battery cells including thin film/microbattery, flexible, cylindrical and prismatic; andbattery packs and systems.

o Post Li-ion BatteriesBattery technologies including redox-flow batteries, sodium-ion, lithiumsulfur, lithium-air, and magnesium-ion, and their supply chains, including electrodes, electrolytes,battery cells and battery packs/systems.

o Solid-State BatteriesSupply chain including electrodes, battery cells, battery packs/systems andelectrolytes, including polymer, inorganic and inorganic/polymer, inorganic materials,including argyrodites, LIthium Super Ionic CONductor, (LISICONs), Thio-LISICONs,sulfide glasses, oxide glasses, perovskites, anti-perovskites and garnets.

o RF Acoustic Wave FiltersIncluding Surface Acoustic Wave (SAW), Temperature Compensated (TC)- SAW, BulkAcoustic Wave- Free-standing Bulk Acoustic Resonator (BAWFBAR), BAW-Solidly-Mounted Resonator (BAW-SMR), and Packaging.

o RF Power AmplifiersIncluding Low Noise Amplifiers, Doherty Amplifiers, Packaging, and Millimeter-Wavetechnology.

o RF Front-End Modules

o MicrofluidicsFrom components to chips and systems, including all applications.

About Yole Développement | www.yole.fr | ©2019

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I-MICRONEWS MEDIA

To meet the growing demand for market,

technological and business information,

i-Micronews Media integrates several tools

able to reach each individual contact within its

network.

We will ensure your company benefits from

this

ONL INE ONS ITE INPERSON

i-Micronews e-newsletter

i-Micronews.com

FreeFullPDF.com

Events Webcasts

Unique, cost-effective ways

to reach global audiences.

Online display advertising

campaigns are great strategies

for improving your

product/brand visibility. They

are also an efficient way to

adapt with the demands of the

times and to evolve an effective

marketing plan and strategy.

Brand visibility, networking

opportunities

Today's technology makes it

easy for us to communicate

regularly, quickly, and

inexpensively – but when

understanding each other is

critical, there is no substitute

for meeting in-person. Events

are the best way to exchange

ideas with your customers,

partners, prospects while

increasing your brand/product

visibility.

Targeted audience

involvement equals clear,

concise perception of your

company’s message.

Webcasts are a smart,

innovative way of

communicating to a wider

targeted audience. Webcasts

create very useful, dynamic

reference material for

attendees and also for

absentees, thanks to the

recording technology.

#15,800+ monthly unique visitors

on i-Micronews.com

#10,900+ weekly readers

of i-Micronews e-newsletter

#110 attendees on average

#7+ key events planned for 2019

on different topics

#380 registrants per webcast on

average to gain new leads for

your business

Contact: Camille Veyrier ([email protected]), Marketing & Communication Director

About Yole Développement | www.yole.fr | ©2019

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CONTACT INFORMATION

o CONSULTING AND SPECIFIC ANALYSIS, REPORT BUSINESS

• North America:

• Steve LaFerriere, Senior Sales Director for Western US & Canada

Email: [email protected] – + 1 310 600-8267

• Chris Youman, Senior Sales Director for Eastern US & Canada

Email: [email protected] – +1 919 607 9839

• Japan & Rest of Asia:

• Takashi Onozawa, General Manager, Asia Business Development

(India & ROA)

Email: [email protected] - +81 34405-9204

• Miho Ohtake, Account Manager (Japan)

Email: [email protected] - +81 3 4405 9204

• Itsuyo Oshiba, Account Manager (Japan & Singapore)

Email: [email protected] - +81-80-3577-3042

• Korea: Peter Ok, Business Development Director

Email: [email protected] - +82 10 4089 0233

• Greater China: Mavis Wang, Director of Greater China Business

Development

Email: [email protected] - +886 979 336 809

• Europe: Lizzie Levenez, EMEA Business Development Manager

Email: [email protected] - +49 15 123 544 182

• RoW: Jean-Christophe Eloy, CEO & President, Yole Développement

Email [email protected] - +33 4 72 83 01 80

o FINANCIAL SERVICES (in partnership with Woodside Capital

Partners)

• Jean-Christophe Eloy, CEO & President

Email: [email protected] - +33 4 72 83 01 80

• Ivan Donaldson, VP of Financial Market Development

Email: [email protected] - +1 208 850 3914

o CUSTOM PROJECT SERVICES

• Jérome Azémar, Technical Project Development Director

Email: [email protected] - +33 6 27 68 69 33

o GENERAL

• Camille Veyrier, Director, Marketing & Communication

Email: [email protected] - +33 472 83 01 01

• Sandrine Leroy, Director, Public Relations

Email: [email protected] - +33 4 72 83 01 89 / +33 6 33 11 61 55

• Email: [email protected] - +33 4 72 83 01 80

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About Yole Développement | www.yole.fr | ©2019