Tech markets trends Biochips Microfluidic chips Yole Feb2003 by HC120522162740

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Technologies and markets trends in biochips and microfluidic
chips

Dr Eric Mounier, Dr Michel Provence,
Contact : mounier@yole.fr



Abstract

This talk gives an overview of the biochips and microfluidics international activities. Regarding
biochips, the market is going from pharmaceutical R&D tools to diagnostic, environment and
agrobusiness analysis. The second generation of products is currently under development with
many technologies in development (guided optics, polymers …). Proteins chips are in
development with a strong position of Europe compared to the USA. It is expected that the
microarrays market will be a multi-billion $ market in 2005. Regarding microfluidics chips, there
is a large panel of technologies used for the manufacturing of components. Materials are
ranging from metal, Si and glass micromachining to polymer microreplication. In Europe, there
is a pioneer activity in polymer micropreplication and the use of microtechnologies for the
manufacture of microfluidic chips will find various applications in proteomics and cells analysis
(current commercialization is for HTS and genomics).



1. Introduction

Since the first biochip developments at the end of the 80’s in large pharmaceutical groups and
associated companies as new research tools, biochips and microfluidic chips have grown as an
industrial field in itself, supplying analytical tools and solutions dedicated primarily to the drug
development research. The most common type of biochips is based on the optical detection of
DNA hybridization and a lot of efforts are currently done to adapt this massively parallel
detection technique to protein and cell chips. As the industrial field matures, the companies are
structuring their DNA chip offer according to various genomes or sets of genes of interest for
pharmaceutical, agricultural and academic research.

However, since the demand of customers is rapidly moving, biochip companies have to be very
flexible on their business model as well as on products and services. At the same time, a
number of technical and economic limiting factors exist for the first generation of biochips that
were introduced on the market. Those limiting factors are the drivers of a new generation of
products to be introduced on the market in the coming months.




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The sample preparation step is increasingly considered as the limiting step in the throughput of
genomic and proteomic experiments. As a result, microfluidic components are developed to
speed up and simplify the sample preparation steps. Both glass / silicon and polymer substrates
are used to develop microfluidic components using technologies derived from the
microtechnology industry. Depending on the targeted applications, various materials and fluid
motion principles can be used.

This report will give an overview of the technologies, applications and markets of biochips and
microfluidic chips in the life science business. The major technologies, as well as markets and
players, are described. Table 1 shows the main data of our analysis.




                                    Microfluidic chips            Biochips
Number       of    manufacturers    30                            49
worldwide
2000 market                         400 million USD            550 million USD
Growth rate                         40 %                       40 %
Expected markets for 2005           2 billion USD              3 billion USD
Current applications                High Throuhput Screening Gene expression profiling,
                                    for pharma R&D             genotyping, sequencing for
                                                               pharma and academic R&D
Emerging applications               Genomics, proteomics, cell Diagnostic for agrobusiness,
                                    analysis                   clinical, personalized therapy



Tableau 1 : Market figures evolution for microfluidic chips and biochips (source Yole)




          Technologies and markets trends in biochips and Microfluidic chips – February 2003 - 2
2. Microfluidics

2.1. Applications and markets

Error! Reference source not found.Figure 1 shows the different applications for microfluidic
components. Today, the first commercialized components are for High Throughput Screening
applications.



                                    Microfluidic components




    High Troughput                                                                 Cell analysis
                              Genomics                  Proteomics
  Screening Hardware


• Miniaturised microtiter
         plates              • Amplification            • Separation              • Cell screening

• Dispensers components       • Separation               • Spraying           • Cell counting / sorting

                                                       • Cristallisation       • Electrophysiology -
                                                                                    transfection



                                                    • Connection to mass
                            • Hybridisation,                                        • R&D and
                                                     spectrometry, X-ray
                              Sequencing                                            Diagnostic
                                                     diffraction, prot-prot
                                                                                   applications
                                                      interaction devices
                                                                                   (Cytometry)




Figure 1 : Microfluidics applications


Today, commercialization in HTS and molecule separation is starting. Regarding the need for
low cost for HTS disposables, there is a consenus on polymer microreplication. Emerging
markets are for genomics and proteomics for pharmaceutics R&D..



2.2. Technologies

Error! Reference source not found.Figure 2 shows the different Technological platform and
the actuation principle for the different companies manufacturing microfluidic chips. “Traditional”
micro-mechanics techniques, such as milling, turning or drilling, are also used for the
components production.




            Technologies and markets trends in biochips and Microfluidic chips – February 2003 - 3
   Technological
     platform                                                       Evotec / Berlin
                        Seyonic                                                         Caliper
                                                                      University

                        Tronic’s                                                       Micralyne
                                                                         Aviva
  Glass / Silicon
                                                                      Bioscience
                       MicroFab                                                        Osmooze

                                                                                         AMIC




                                       Micronics        Tecan
                                                                                      DiagnoSwiss
                                      BioMérieux        Gyros
     Polymer                                                                            Aclara

                                                                AMIC

                          IMM                              Steag Microparts


   Fluid in motion                     External       Centrifugal
                     Piezoelectric                                       Magnetic       Electrical
      principle                        pressure         force




Figure 2 : Microfluidic manufacturing technologies



Regarding the processed material, it is mainly Si/glass and polymer which are equally used. For
example, companies such as Seyonic (CH), Microfab (D) … are processing Si and/or glass
materials while IMM (D), bioMérieux (F), Steag microParts (D), Diagnoswiss (CH) are using
polymers.

The principle for fluid motion can be piezoelectric, can use external pressure, centrifugal force,
magnetic or electrical (electrophoresis) actuation. In Europe, some players such as Steag
microParts (D) or Amic (SW), are mastering different actuation principles.



2.3. Environment

Basically, the microfluidics business model can be split in:
         Components manufacturing service
         Tooling service
         Systems manufacturing

Europe is rather service-oriented while USA has both the service and system approach. Many
microtechnology European players are manufacturing microfluidic chips using micro-replication :
Steag microParts (D), Mildendo (D), Bartels (D), Amic (SW), Gyros (SW), DiagnoSwiss (CH).




           Technologies and markets trends in biochips and Microfluidic chips – February 2003 - 4
Some companies also use conventional polymer replication for manufacturing (Weidmann
Plastics and Leister Process Technologies in Switzeralnd, NUNC in Denmark …

In Asia, the activity is mainly located in Japan with limited industrial activity outside Japan. The
developments are made through collaborations between companies and laboratories with
support from the Ministry of Economy, Trade and Industry.

The situation is dramatically different in the USA where there is a strong funding from private
investors. The technological offer is wider than in Europe with technological platform for
replication in polymers, glass and Si. The launching of products on the market is made through
collaborations involving instrumentation companies (Caliper and Agilent, Micronics and
Honeywell …).



3. Microarrays

3.1. Applications and market

First marketed in the mid-90’s, the current market for DNA microarrays is mainly pharmaceutical
and academic R&D for gene expression profiling, genotyping and sequencing. Others R&D
markets are agrobusiness, environment and diagnostic. Clinical diagnostic, agrobusiness
analysis and personalized therapy are expected growing markets in the years to come. The
growth rate in the coming years is expected to be between 30 and 50 %. Regarding protein
microarrays, they are at early stage for commercialization.

In 2000, the microarrays market was about 500 million USD. According to UBS Warbug, the
market distribution is shown on Error! Reference source not found.Figure 3.


                            Integrated
                             Systems                           Scanners
                               26%                               30%




                      Softw are
                         3%

                         Arrayers                     Chips / slides
                           11%                            30%



Figure 3 : Microarrays market distribution



3.2. Technologies

Error! Reference source not found.Figure 4 shows the technologies vs. the approximate
number of probes per chip (low is less than 1 000, medium is 1 000 to 10 000 and high is more
than 10 000). Today, the second generation of products and services are under development.

          Technologies and markets trends in biochips and Microfluidic chips – February 2003 - 5
However, there are still technical and economic factors affecting the development of DNA
microarrays, they are: the need for better sensitivity, the flexibility, the cost (therefore there is a
move to polymer for lowering the cost), the speeding of hybridization and the integration of
fluidics on the chips itself.


    Technology
    maturity
                                                                                           In-situ synthesis –
                                   Mechanical Spotted slides – Opto detection                Opto detection
                                  (Genomic solutions, Morotola, Agilent, MWG                   (Affymetrix,
                                       Biotech, Takara, Eurogentec ...)                         Agilent…)




         Silicon components
     + Electrochemical detection                                           In house in-situ synthesis -
       Xanthon - Motorola - Apibio -                                       Opto detection (Nimblegen,
      Cantion - Toshiba - IBM Zurich                                       Febit …)
                                  New manufacturing concepts – Opto detection
           Silicon
        components +                                       Stamping - BioCept, Corning
           Optical
                                         Virtual Arrays - Illumina, Luminex, Smart Beads
          detection
          Nanogen –                          Flow through chips - Pamgene , Metrigenix
         Combimatrix -
            Apibio                            Polymer chips - Exiqon / Steag Microparts

            Low                                       Medium                                     High
                                1000                                            10 000

                                        Number of probes / component




Figure 4 : DNA microarrays technologies



3.3. Environment

Today, there is a strong position of the USA on the DNA microarrays and Affymetrix is still
leader with 40% market share. Moreover, there is the presence of large groups such as
Motorola, Corning … with high investments from VCs.

European players are present both in DNA microarrays with MWG Biotech (D), Memorec (D),
Apibio (F), Genescan Europe (D), OGT (UK), Zeptosens (CH), Qiagen (NL), Eurogentec (B),
Pamgene (NL) and Cantion (DK) and in chemical / protein arrays with Graffinity
Pharmaceuticals (D), OGS (UK), Zeptosens (CH), Biacore (SW), Affinity Sensors (UK) …
Europe has a lower DNA microarray activity than USA but is more advanced in protein
microarrays development. Asia has both a weak commercial activity on DNA microarrays.
Moreover, Asia is technically behind Europe and USA. The Japan government has launched an
initiative in 2001. And Asian companies have agreements with others non-Asian companies
(Olympus and Pamgene, Hitachi Genetic Systems and Nanogen …).




           Technologies and markets trends in biochips and Microfluidic chips – February 2003 - 6
At the industrial level, the business models are evolving. Microarrays manufacturers are
gradually evolving towards drug delivery service providers, instrumentation suppliers and drug
candidate suppliers. Moreover, many merging and acquisitions have been realized.




4. Conclusions

Regarding microfluidics chips, there is a large panel of technologies used for the manufacturing
of components. Materials are ranging from metal, Si and glass micromachining to polymer
microreplication. In Europe, there is a pioneer activity in polymer micropreplication and the use
of microtechnologies for the manufacture of microfluidic chips will find various applications in
proteomics and cells analysis (current commercialization is for HTS and genomics). Regarding
biochips, the market is going from pharmaceutical R&D tools to diagnostic, environment and
agrobusiness analysis. The second generation of products is currently under development with
many technologies in development (guided optics, polymers …). Proteins chips are in
development with a strong position of Europe compared to the USA. It is expected that the
microarrays market will be a multi-billion $ market in 2005.

This article presents a short view of the Yole Développement report: BioFab. This report gives
an overview of the biochips, microfluidics and biosensors international activities. It describes
players, technologies as well as applications, markets volumes, technological trends and
limiting factors. It also gives more than 130 worldwide player profiles.




         Technologies and markets trends in biochips and Microfluidic chips – February 2003 - 7

								
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