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Microarray Solutions
                                                The SCHOTT Nexterion® Newsletter                           N° 1
                                                                                                          March 2006

Page 2 to our first issue of the “Microarray Solutions” newsletter, designed to keep members of the life sci-
Welcome               Foreword by Dr. Lutz Wehmeier (General Manager)
ences community informed history developments at SCHOTT Nexterion® and to highlight some of the interesting
                      Short about of SCHOTT Nexterion®
microarray applications that our products are currently being used for.
Page 3              Nexterion® HiSens Slides
                    “Signal and sensitivity enhancement through an optical interference coating for
                    DNA and protein microarray applications” is the title of new scientific paper written
                    by Dr. Rajendra Redkar, R&D Scientist at SCHOTT Nexterion® in Duryea, PA.
                    “Microarray Solutions” gives you an insight into some of the key elements behind this pa-
                    per and explains why users are reporting up to an 8x increase in signal intensity over
                    regular slides with the new HiSens slides from SCHOTT Nexterion®.

Page 4              Ambion HiSens E evaluation produces “incredible” results
                    A report on Ambion's recent evaluation of Nexterion HiSens E slides with its miRNA probe
                    set in which it saw an average 8 fold increase in signal intensity over regular glass slides,
                    leading the company to declare that SCHOTT "has developed another premier microarray
                    substrate."

Page 5              Microplates for arraying
                    Ever thought about using the microtiter plate format for high throughput arraying?
                    Are you unhappy about the performance of 96 well polymeric and glass bottom
                    plates on the market? Not sure if your arrayer is capable of arraying into plates or
                    need advice on suitable microplate scanners?
                    Alistair Rees (International Product Manager for Coated Substrates) discusses the new
                    Nexterion® MTP 96 microplate and highlights some of the compatible arrayers and scan-
                    ners available on the market.

Page 7              New Product Developments
                    • New Surfaces for Protein and Glycan Microarrays
                    • New and Improved Slide Storage Boxes for Microarray Slides

Page 8              Technical Support in Focus
                    Having problems with signal intensity and or too high background? Interested in increas-
                    ing spot size or improving spot morphology? Looking at ways to reduce the number of
                    protocol steps? SCHOTT Nexterion® prides itself on offering the best technical support to
                    customers and starting in the next edition, “Microarray Solutions” will bring you a section
                    focusing on the most interesting trouble shooting issues addressed by our technical sup-
                    port team and a Q&A section dedicated to tech support questions received from our read-
                    ers.

Page 9              In October 2004, SCHOTT Nexterion® opened what it considers to be the most mod-
                    ern and hi-tech microarray slide production facility in the world.
                    Production Director Christian Jabschinsky gives you an overview of the challenges
                    SCHOTT faces to produce the highest quality microarray substrates and gives you a be-
                    hind the scenes insight into how this multi-million dollar facility operates.

Page 11             Conference and Exhibition Calendar 2005/06
page 2                                                                         Microarray Solutions


                                   Foreword

                                   SCHOTT Nexterion® has come a long way since our formation back in
                                   October 2002. For those of you who are not familiar with our story, here
                                   is a brief overview of the changes that have occurred at Nexterion® over
                                   the past few years. The SCHOTT Nexterion® unit was created as a result
                                   of the Vision 2010 project during which the SCHOTT unit identified poten-
                                   tial new market segments that had high growth potential. Nexterion® Slide
                                   A, one of the Aminosilane coated slides in our portfolio, was the first
                                   product to be launched by the company in 2002. I joined the company
                                   soon after as General Manager in 2003 having spent several years run-
                                   ning the microarray business at MWG Biotech. We spent the next few
                                   months working hard to integrate the microarray slide business that had
                                   been acquired from Quantifoil, which resulted in the addition of several
                                   new surface chemistries and reagents being added to our portfolio. Just
                                   12 months later saw the completion of our new multi-million Euro slide
                                   production facility in Jena, where all Nexterion® products are now manu-
                                   factured using modern, state-of-the-art technology. We also relocated the
                                   Nexterion® business unit from the SCHOTT corporate headquarters in
                                   Mainz to SCHOTT Jenaer Glas in Jena. Jena is an award-winning bio-
                                   technology hotspot in Germany offering Nexterion® potential synergies
                                   with other biotech companies, as well as close links with the life science
                                   driven academic community, making it an ideal location for our microar-
                                   ray business.
                                   Nexterion® has grown rapidly since 2002 and we are now proud to offer
                                   the broadest range of high quality substrates for DNA and protein arrays,
                                   both in a slide a microplate format. We have the privilege of supplying
                                   microarray consumables to some of the most important microarraying
            Dr. Lutz Wehmeier      sites in the world and our aim to introduce exciting and innovative
            General Manager
            SCHOTT Nexterion®      products into the microarray substrate market resulted this year in the
                                   launch of the MTP 96 microplate array format, a natural progression from
                                   our Multiplex (MPX) 16 and 48-well formats, and our new signal
                                   enhancing slide coating called HiSens. We have very high expectations
                                   for both products and will continue to strive to offer our customers the
                                   most innovative, forward-thinking microarray consumables.
                                   During 2005, SCHOTT Nexterion also entered into a number of
                                   collaborations with high-profile life sciences companies in the US and
                                   Europe and this is set to continue in 2006. A co-marketing agreement
                                   with Operon was signed in 2005 and resulted in the launch of a kit of
                                   slides and processing reagents optimized around the Operon 70 mer
                                   oligonucleotides. We also recently finalized a co-marketing agreement
                                   with Genomic Solutions and Alpha Innotech to promote arraying into
                                   microplates and will be organizing joint workshops with these two
                                   companies later this year. Several other important collaborations have
                                   been established behind the scenes, some of which will be announced
                                   before the end of the year, and these relationships clearly demonstrate
                                   the outstanding reputation SCHOTT Nexterion is developing throughout
                                   the world for microarray substrates and consumables.
                                   We are excited about the future of SCHOTT Nexterion®, and hope that
                                   you will enjoy future issues of this e-newsletter as we update you on fur-
         SCHOTT JENAer GLAS GmbH
                                   ther developments. In this edition of “Microarray Solutions”, you will find
                                   articles on our new range of HiSens and MTP products, plus some inter-
                                   esting information about our state-of-the-art production facility in Jena.
                                   We have also included a feature on Ambion and their miRNA probe sets
                                   and how HiSens slides have really changed the way of thinking at Am-
                                   bion. If you have suggestions about ways to make these updates more
                                   effective or articles you would like to see, please feel free to contact
                                   Karola at karola.koban@schott.com.
                                   Regards,
                                   Dr. Lutz Wehmeier
Microarray Solutions                                                                                      page 3




                                      Nexterion® HiSens Slides
                                      Limitations of Regular Slides for Certain Applications
                                      Microarray technology has been accepted as a preferred gene expres-
                                      sion tool in basic science research such as genotyping, metabolic path-
                                      ways, cancer research, toxicology, and functional genomics. Because
                                      this technology utilizes thousands of DNA/antibody probes representing
                                      the genome or proteome, it can be used for simultaneous detection and
                                      identification of organisms as it offers several important advantages over
 “Signal and sensitivity en-          the standard PCR and ELISA-based detection methods. However, mi-
 hancement through an optical         croarray technology has struggled to its logical progression into the diag-
 interference coating for DNA         nostic field due to a lack of standardization. One such problem is the lack
 and protein microarray appli-        of sensitivity of the microarray data, making it difficult to separate the
 cations” is the title of new         experimentally induced variation from the true biological results. In many
 scientific paper written by Dr.      instances the amount of RNA is limiting and the activity of low expressing
 Rajendra Redkar, R&D Scien-          genes such as regulatory transcription factors may not be clearly quanti-
 tist at SCHOTT Nexterion® in         fiable. Alternative labeling systems, signal amplification methods and
 Duryea, PA.                          detection technologies have all been developed in an attempt to increase
                                      the microarray sensitivity. However these alternatives are not cost-
 “Microarray Solutions” gives you     effective and/or require cumbersome procedures, often deviating away
 an insight into some of the key      from standard protocols that researchers are comfortable with. The new
 elements behind this paper and       HiSens slides from SCHOTT Nexterion® offer a cost-effective solution to
 explains why users are reporting     the sensitivity issue and are compatible with routinely used microarray
 up to an 8x increase in signal       equipment and protocols, which coupled with higher detection sensitivity
 intensity over regular slides with   could be critical in developing diagnostic assays.
 the new HiSens slides from
 SCHOTT Nexterion®.                   Optical Interference Coating to Increase Signal Intensity
                                      The optical interference coating deposited on the HiSens slides is com-
                                      prised of a multi-layered, dielectric, thin-film interference coating. The
                                      optical interference coating was carefully optimized to yield a product with
                                      consistent quality that could easily be integrated into SCHOTT Nexte-
                                      rion®’s large-scale production facility in Jena. Several specific production
                                      steps were developed to maintain the integrity of the optical interference
                                      coatings. Briefly, the thin-film dielectric coating works on the phenomenon
                                      of optical interference, which can be either constructive or destructive. By
                                      design, the interference is made constructive to enhance the photoab-
                                      sorption of the Cy3 and Cy5 dyes at the surface or in the vicinity of the
                                      surface (within ~60 nm from of the substrate), and also to reflect and
                                      redirect the microarray fluorescence signals toward the detector during
                                      scanning. The HiSens slide, therefore, differs from slides with metallic
                                      coatings that are currently on the market where the signal is only en-
                                      hanced due to reflection.
                                      Validation experiments with HiSens slides have shown a greater than
                                      eight-fold signal amplification in both Cy3 and Cy5 channels, thus provid-
                                      ing an order of magnitude increase in signal intensity. This leads to sig-
                                      nificantly higher signal-to-noise ratios in microarray experiments. Any
    Nexterion® HiSens Slides          functional coating (Epoxysilane, Aminosilane etc.) can be applied on top
                                      of the optical interference coating for subsequent biomolecular attach-
                                      ment and consequently the HiSens slides can be used in place of tradi-
                                      tional slides without any protocol modifications. The HiSens slides have
                                      been tested using contact and non-contact microarray printers, as well as
                                      laser and CCD-based scanners, and have proven to be fully compatible
                                      with most commercially available microarray equipment.

                                      HiSens for Different Applications
                                      According to Alistair Rees, International Product Manager for Coated
                                      Slides, a wide range of applications are likely to benefit from the use of
                                      the HiSens slides. For example, applications in which researchers have
                                      only a limited amount of target material, or in which amplification of mate-
page 4                                                                                Microarray Solutions


                                         rial is difficult or problematic. The latter includes measurement of biopsy
                                         samples and miRNA (see Ambion article below), as well as gene expres-
                                         sion monitoring and diagnostics involving weak signals.

                                         SCHOTT Nexterion® officially launched the Nexterion® HiSens slides in
                                         January with the Nexterion® Slide A (Aminosilane) and Nexterion® Slide
                                         E (Epoxysilane) functional coatings. HiSens slides will be available with
                                         other Nexterion® surface chemistries in the near future.

                                         Dr. Rajendra Redkar's paper "Signal and sensitivity enhancement
                                         through optical interference coating for DNA and protein microarray
                                         applications" can be seen in full at the citation Journal of Biomolecular
                                         Techniques 17(2): 122-130 (2006).


                   Ambion HiSens study produces “incredible” results
                                         Ambion’s mirVana miRNA Probe Set is a collection of amine-modified
                                         DNA oligonucleotides targeting a comprehensive selection of human,
                                         mouse, and rat miRNAs from miRBase. Developed in conjunction with
 “HiSens E provided incredible           the mirVana™miRNA Labeling Kit, the mirVana miRNA Probe Set is de-
 signal and high signal-to-noise,        signed for preparation of “miRNA arrays” on glass slides. Previously
 even with significantly lower tar-      Ambion, Inc. had used the Nexterion® Slide E epoxy slides to produce the
 get concentration… and provided         miRNA arrays with great success. Ambion’s familiarity with the Slide E
 an average of 8 fold increase in        surface chemistry made them the perfect candidate to test the new
 signal intensity (over regular          HiSens E slides and Jeffrey Shelton in the R&D Division at Ambion was
 slides)” – Jeffrey Shelton of Am-       sent some of the very first HiSens slides produced by SCHOTT to evalu-
 bion, Inc.                              ate.
                                         In the evaluation, the mirVana miRNA probes were printed onto 25
                                         SCHOTT Nexterion® Slide E slides and 25 HiSens Slide E slides on the
                                         same print run. The miRNA fraction from 20 µg, 5 µg, and 2 µg of RNA
                                         from human bladder and lung were labeled using the mirVana™ miRNA
                                         Labeling Kit, and fluorescent dyes were attached using standard coupling
                                         procedures. The fluorescently labeled bladder and lung miRNA were
                                         mixed and hybridized on duplicate arrays for each substrate type.
  Slide E vs HiSens E 20 ug eq bladder   “The HiSens slides provided an average of 8 fold increase in signal inten-
  vs lung miRNA tested by Ambion         sity for each starting mass equivalent, with no detectable loss of signal to
                                         noise ratios. The signal I obtained from the 2µg equivalents was much
                                         greater than I had ever seen for that starting mass amount. I normally
                         Nexterion®      had to use greater than 20µg equivalents to obtain an equivalent signal
                         Slide E         on the Slide E or similar substrates,” Jeffrey Shelton reported.
                                         Shelton went on to say, “The amine-modification of the mirVana miRNA
                                         probes makes them ideally suited for use with epoxy or aldehyde surface
                                         chemistries. We have recommended SCHOTT Nexterion® Slide E mi-
                                         croarray slides as they are convenient, easy to use, and provide consis-
                         Nexterion®      tent results. However, since this evaluation, it is our intention to recom-
                         HiSens E        mend the Nexterion® HiSens E to customers who wish to maximize the
                                         signal from small starting mass RNA fractions. With HiSens E, SCHOTT
                                         Nexterion® has developed another premier microarray substrate.”
                                         Although other microarray slides claiming to enhance signal intensity
                                         have appeared on the market in the past, with some still commercially
                                         available today, this type of slide has failed on the whole to take off with
                                         users typically complaining of poor slide reproducibility, long lead times to
                                         get hold of the slides and usually a very high price. “I have tried other
                                         manufacturers’ reflective substrate slides in the past and was not at all
                                         impressed”, continued Shelton. “I went into this beta test of HiSens E
                                         somewhat skeptical, but now I’m your newest customer! The HiSens E
                                         slides provided incredible signal, high signal-to-noise, and no significant
                                         increase in background.”
Microarray Solutions                                                                                        page 5



                                       The results of the HiSens evaluation carried out by Ambion clearly dem-
                                       onstrate that HiSens slides could be an invaluable tool for applications in
                                       which researchers have only a limited amount of target material, or in
For further information on Ambion,     which amplification of material is difficult or problematic. This is particu-
 Inc. and its range of products, in-   larly the case for miRNA microarrays because the miRNA is only a minor
cluding the mirVana miRNA Probe        part of the whole RNA fraction (around 1/10000), but HiSens could also
Set, please visit the Ambion web-      be a useful tool for biopsy samples, as well as gene expression monitor-
      site at www.ambion.com           ing and diagnostics involving weak signals. Many signal amplification
                                       techniques have been developed in recent years to combat this problem
                                       but most of these techniques raise questions about biased amplification
                                       that could ultimately affect the quality of the experimental results. With
                                       Nexterion® HiSens slides, these concerns are eliminated and Ambion is
                                       likely to be the first of many customers to benefit from this exciting new
                                       technology from SCHOTT Nexterion.

                                       Microplates for arraying
                                       Although the microtiter plate format has been a standard research tool for
                                       clinical diagnostics and drug discovery for some time, it still has not be-
 Ever thought about using the          come a popular microarray tool despite the recent introduction of high-
 microtiter plate format for high      resolution plate scanners and compatible arrayers. Feedback from the
 throughput arraying, but un-          market, however, seems to indicate that this technology may finally be
 happy about the 96 well poly-         coming to the fore and many companies are now actively looking to intro-
 meric and glass bottom plates         duce products that will allow users to pursue high-throughput microarray-
 on the market? Not sure if your       ing with the microtiter plate format.
 arrayer is capable of arraying
 into plates or need advice on         SCHOTT’s new 96-well glass bottom microtiterplates are the result of two
 suitable microplate scanners?         years of development work at one of SCHOTT Nexterion®’s R&D Centers
                                       of Excellence in Duryea, PA and were developed in response to market
 Alistair Rees (International Prod-    demand, which indicated that there were numerous limitations with con-
 uct Manager for Coated Sub-           ventional 96 well polymeric and existing glass bottom microtiter plates
 strates) discusses the new Nex-       utilized in microarraying.
 terion® MTP 96 microplate and
 highlights some of the compatible     Some of the weaknesses identified in these existing products included:
 arrayers and scanners on the          • Printable area per well: microarray print heads cannot access the
 market.                                 entire well plate area because the wells are recessed, thus limiting the
                                         number of features per well and arrayer compatibility.
                                       • Print time: the depth of the wells, and the subsequent additional Z-
                                         axis travel, makes printing time consuming.
                                       • Well contamination: the intra-well print area may be restricted due to
                                         the contamination of the well edges with bonding adhesive. In addi-
                                         tion, adhesive out-gassing can affect functional coating performance.
                                       • Coating range & uniformity: difficulty in uniformly applying functional
                                         coatings to three dimensional polymeric microtiter plates.
                                       • Plate flatness: conventional microtiter plates suffer from poor optical
                                         transparence and flatness.

                                       In collaboration with a high-profile biotech company in the San Francisco
                                       Bay Area, and in consultation with several customers in Europe and the
                                       US, SCHOTT Nexterion® took up the challenge of designing a product
                                       that eliminated the key weaknesses outlined above and offered its own
                                       unique characteristics to assist customers. Dan Haines, Advanced Mate-
      Nexterion® Microtiterplate Kit   rials & Coatings Research Scientist at Schott North America in Duryea,
                                       PA and head of the team that designed the Nexterion® MTP microarray
                                       products, is extremely satisfied with the final product design. “We are
                                       excited to provide a new research platform that combines our high quality
                                       coatings with an innovative 96-well microtiter plate design that makes the
                                       transition from (multiplexed) microscope slides to microtiter plates seam-
                                       less. The low-fluorescent glass plate can be printed/processed/scanned
                                       without it ever being removed from its tray for those users desiring high
page 6                                                                           Microarray Solutions


                                    throughput – alternatively, the plate can be quickly and easily re-
          ®                         moved/inserted depending on the experimental protocols and equipment
 Nexterion MTP 96 Microtiterplate
     Kit consists of three main     available to the researcher. Well contamination problems are resolved by
            components              use of a recessed adhesive on the superstructure that preferentially binds
                                    to the hydrophobic patterning material. The removable superstructure
                                    allows for unencumbered full area printing of the wells while allowing
                                    hybridization and wash volumes up to 200 µl/well. This platform has
                                    been validated both by our customers and equipment partners Alpha
                                    Innotech and Genomic Solutions. For a researcher desiring higher ex-
                                    perimental throughput while maintaining current slide-based protocols
                                    and procedures, the Nexterion® MTP platform provides a flexible tool.”

               Glass Plate          Nexterion® MTP 96 consists of three main components: a microarray
                                    quality patterned glass substrate, a 96-well silicone superstructure and a
                                    microtiter plate tray support. It is available as a complete kit or as sepa-
                                    rate components, with the glass substrates offered with either the Slide E
                                    (Epoxy) or Slide A (Aminosilane) functional coatings or as uncoated glass
                                    for custom applications. The Nexterion® MTP 96 design fully conforms to
                                    SBS (Society for Biomolecular Screening) standards and is suitable for
                                    high-throughput robotic handling. One of the major benefits of the Nexte-
              Superstructure        rion® MTP 96 plate is that the design of the kit components allows the
                                    plate to be used in any make of microplate arrayer. Over 1000 spots can
                                    be printed into each of the 96 wells due to the larger effective well area
                                    (49mm2) and printing time is significantly reduced as the printing pins are
                                    subject to less Z axis travel compared to conventional 96 well microtiter
                                    plates.

                                    Microplate Array Printers
                                    Modern robotic arrayers, both contact and non-contact, are already
                                    equipped to handle the 96-well format and many have pre-programmed
          Tray, lid, fixing pins    definitions for the Nexterion® MTP 96 plates, thus simplifying set up.
            and sealing film
                                    However it may be necessary to purchase additional array control soft-
                                    ware and a replacement arraying bed to hold the microplates during print-
                                    ing.

                                    The following table details arrayers can be modified to array into mi-
                                    croplates:

                                    Arrayer                                    Deposition       Destination
                                                                                method          microplate
                                    Arrayjet AJ120                             Non-contact           20
                                    Aushon Biosystems 2470                     Contact               20
                                    Bio-Rad BioOdyssey Calligrapher            Contact               2
                                    Bio-Rad VersArray ChipWriter Pro           Non-contact           1
                                    GeneMachines OmniGrid Accent               Contact               6
                                    Genetix QArray2                            Contact               16
                                    Genetix QArray mini                        Contact               4
                                    Genomic solutions MicroGrid                Contact               16
                                    Lab Next Xact                              Contact               2
                                    Lab Next THOMAS™                           Contact               9
                                    PerkinElmer Piezorray                      Non-contact           5
                                    Scienion sciFLEXARRAYER                    Non-contact           4
                                    Telechem NanoPrint™                        Contact               12

                                    The Genomic Solutions arrayers have defined parameters for the Nexte-
                                    rion® MTP 96 microplates in the plate arraying software. A software up-
                                    grade is available from Genomic Solutions to accommodate the switch
                                    from slides to Nexterion® MTP 96 for the OmniGrid Accent model.
Microarray Solutions                                                                                                  page 7



                                                 Microplate Scanners
                                                 Arguably the biggest obstacle to the wider use of microplate arrays has
                                                 been the lack of access to microplate compatible high-resolution scan-
                                                 ners. A number of suitable scanners are now commercially available and
                                                 the following table details some of the scanners that are compatible with
                                                 the Nexterion® MTP 96 microplate:

                                                 Manufacturer                            Model
                                                 Alpha Innotech Corporation              NovaRay® Detection Platform
                                                 Blueshift Biotechnologies, Inc          IsoCyte™ laser scanning
                                                                                         fluorimeter
                                                 TECAN                                   Laser Scanner

                                                 The Alpha Innotech NovaRay® Detection Platform is compatible with both
                                                 slides and microplates and offers multi-spectral imaging with eight emis-
                                                 sion wavelengths. A less well-known system is the IsoCyte™ Benchtop
 NEXTERION NEWSFLASH!                            Laser Scanner from Blueshift Biotechnologies in Sunnyvale, CA. The
                                                 scanner was developed for high throughput analysis of array-, bead- or
 US Government Awards SCHOTT $1M
 to Develop Microarray Platform for              live cell-based assays in microplates and on slides and the company
 Pathogen Detection                              claims that the system can scan a microplate such as Nexterion® MTP 96
                                                 is less than two minutes. According to Blueshift Biotechnologies, the sys-
 The US government has allotted $1               tem accomplishes this task by fast “object” characterization (e.g. spots or
 million of its defense appropriations bill to
 Schott North America to develop a mi-           cells) and unique imaging in the fluorescence polarization domain.
 croarray-based platform for detecting
 biological agents, Schott said recently.        SCHOTT Nexterion® recently partnered with Genomic Solutions and
 According to Duryea, Penn.-based Schott
                                                 Alpha Innotech at the Plant & Animal Genome Conference in San Diego,
 NA, the funding was secured through the         CA to demonstrate the ease of use and flexibility offered by the Nexte-
 offices of Congressman Paul Kanjorksi           rion® MTP 96 system and its compatibility with the Genomic Solutions
 (D-Penn.). Schott will collaborate with the
                                                 MicroGrid and OmniGrid arrayers and the NovaRay® Detection Platform
 University of Scranton's Institute of Mo-
 lecular Biology and Medicine to develop         from Alpha Innotech. Jeremy Clarke, Global Product Manager at Ge-
 the fully automated and multiplexed             nomic Solutions, was impressed by the level of interest shown at the
 microarray platform, the company said.          conference and clearly feels that the MTP format is now seriously being
                                                 considered as a suitable tool for high-throughput microarraying. “The
 The new platform would be a 96-well
 microarray, with the potential to screen        presentation was well attended and significant interest in the products
 for up to 2,000 pathogens in each well,         from all three companies was registered by attendees, both during and
 Schott said.                                    after the event, suggesting that the microtiter plate format is finally being
                                                 considered by researchers as a serious microarray tool for the near fu-
                                                 ture”, Clarke told “Microarray Solutions”. All three companies are commit-
                                                 ted to continuing this relationship in an effort to promote microplates and
                                                 three further workshops are planned for the US in May in San Francisco,
                                                 CA, Houston, TX and Boston, MA. Clarke went on to say, “We are look-
                                                 ing forward to continuing our relationship with SCHOTT Nexterion® and
                                                 Alpha Innotech. Together, we offer a range of complementary products
                                                 which provide the best solution for fulfilling the new protein arraying work-
                                                 flow”.

                                                 Details of the forthcoming workshops with Genomic Solutions and Alpha
                                                 Innotech will be available soon, including an agenda and list of invited
                                                 speakers for the three locations. Please contact Karola at coatedsub-
                                                 strate@schott.com for further information.
page 8                                                                                Microarray Solutions


                                          New Product Developments


                                          SCHOTT Nexterion® to Develop New Surfaces for Protein and Gly-
                                          can Microarrays
                                          In consultation with customers and collaborators, SCHOTT Nexterion®
                                          has identified protein and glycan microarrays as promising applications
                                          with large growth potential for the future. The feedback that we have re-
                                          ceived from the market so far indicates that one of the biggest challenges
                                          facing customers is the directed immobilization of probe molecules and
                                          SCHOTT Nexterion® is now focusing some of its R&D efforts on identify-
                                          ing suitable surfaces to resolve this issue.
                                          We are also looking to expand our product portfolio by offering additional
                                          surfaces for direct immobilization of different probe molecules, for exam-
                                          ple His-tag, maltose binding protein or lectin coatings. We are very inter-
                                          ested in getting feedback from customers on what type of surfaces they
                                          would like to see offered by SCHOTT Nexterion® in the future. Please
                                          feel free to send your suggestions to us and one of our R&D team mem-
                                          bers will contact you to discuss your ideas in greater detail. Please sub-
                                          mit your ideas to coatedsubstrate@schott.com and help develop the next
                                          generation microarray slide surfaces!

                                          SCHOTT Nexterion® Announces New and Improved Slide Storage
                                          Boxes for Microarray Slides

                                          SCHOTT Nexterion® has introduced a new 25-slide storage box for its
                                          microarray slides which will replace the current 5-slide mailers used for
                                          Nexterion® Slide A+ and AL. This new rigid slide box does not shed plas-
                                          tic particles or outgas plasticizer and allows SCHOTT Nexterion® to send
                                          the products in 25-slide storage boxes. Unique design features include
                                          tabs that are moulded into the lid to prevent the glass substrates from
                                          moving, thus reducing the risk of breakage during transportation, and a
    New Nexterion® 25-slide storage box   new hinge lid with a catch which prevents accidental opening of the stor-
                                          age box.
Microarray Solutions                                                                                       page 9



                                        Technical Support in Focus


          Name: Ruediger Dietrich
                                        Having problems with signal intensity and or too high background? Inter-
          Location: Jena
                                        ested in increasing spot size or improving spot morphology? Looking at
          Job Details: Director R&D     ways to avoid certain protocol steps? SCHOTT Nexterion® prides itself on
          and Tech Support              offering the best technical support to customers. That’s why we will bring
          Likes: good food              you a section with the most interesting troubleshooting issues addressed
          Dislikes: bad food            by our technical support team starting in next edition of “Microarray Solu-
          Interests: hiking, skiing,    tions”. In addition, we planned to include a Q&A section dedicated to tech
          kayaking, preparation of      support questions received from our readers.
          food like cheese, marinated
          herrings, sauerkraut etc.
                                        Meet Nexterion’s Technical Support Team - Dr. Ruediger Dietrich, Direc-
                                        tor of R&D at the SCHOTT Nexterion HQ in Jena, Germany and Mike
                                        Wotring, R&D Scientist at one of SCHOTT’s R&D Centers of Excellence
                                        in Duryea, PA. As Nexterion’s Technical Support Specialists, Ruediger
                                        and Mike are involved with all technical aspects of our product line - from
                                        new product development to protocol optimization, as well as ongoing
          Name: Mike Wotring            customer application support.
          Location: Duryea
          Job Details R&D Scientist     Ruediger and Mike have been active in responding to numerous requests
          Likes: Travel                 for technical support from customers all over the world. Future editions of
          Dislikes: There's never       “Microarray Solutions” will feature some of the most interesting trouble-
          enough time to see every-     shooting issues addressed by Ruediger and Mike, including case studies
          thing!
                                        demonstrating how they responded to a specific customer application
          Interests: Reading, cook-
          ing, hiking, kayaking         issue and were able to help the customer obtain better results. The new
                                        “Technical Support in Focus” section will also allow you to submit your
                                        technical questions to Ruediger and Mike, some of which we will feature
                                        in future editions of “Microarray Solutions”.
                                        Do you have a protocol problem or need help optimizing your microarray
                                        application? Please submit your question to:
                                        coatedsubstrate@us.schott.com
                                        Your question may be featured in future editions of the “Microarray Solu-
                                        tions”.
page 10                                                                               Microarray Solutions


                State of the art Microarray Substrate Production Facility
                                        Q: How long have you worked for SCHOTT? And where do you work
                                        prior to SCHOTT?
                                        I have worked for SCHOTT since September 2003. I transferred when
                                        SCHOTT acquired the microarray business from Quantifoil Micro Tools
  In October 2004, SCHOTT Nex-          who were also based in Jena (Germany). I originally joined Quantifoil just
  terion opened what it consid-         as they started their microarray slide business in May 1999, so I have
  ers to be the most modern and         many years experience in microarray slide production! Prior to Quantifoil,
  hi-tech microarray slide pro-         I studied medical engineering at the University of Applied Science in
  duction facility in the world.        Jena.
                                        Q: How long has SCHOTT been producing microarray substrates?
  Production Director Christian         SCHOTT originally developed and started to manufacture the first Nexte-
  Jabschinsky gives you an over-        rion® microarray product, our Aminosilane coated Slide A, at Duryea in
  view of the challenges SCHOTT         Pennsylvania back in October 2002. At SCHOTT in Jena, we have been
  faces to produce the highest          producing coated slides since October 2004, when we commissioned the
  quality microarray substrates and     new substrate production facility. Virtually all the personal involved in the
  gives you a behind-the-scenes         Quantifoil microarray slide business transferred to SCHOTT when they
  insight into how this multi-million   acquired us. This means that we have microarray slide development and
  dollar facility operates.             production expertise that goes back over seven years.
                                        Q: Why is Jena a good location for SCHOTT's biotech business?
                                        The tradition for scientific based enterprises in Jena goes back to Carl
                                        Zeiss, when in 1846 he created his first workshop here. Much more re-
                                        cently in 1996, the BioRegio network Jena won the German BioRegio
                                        competition with its "bio instrument Jena" concept. The network consists
                                        of established companies like Carl Zeiss and SCHOTT and the younger
                                        companies like Jenoptik, together with over 31 start up companies many
                                        spun off from the University. In addition, there are several major aca-
                                        demic institutes in Jena also involved in the network. We have benefited
                                        from our close cooperation with the University, in particular the Institute of
                                        surface coating, as we have many students on placement working at
                                        SCHOTT.
                                        Q: Can you summarize the production process in your facility?
                                        The first step is glass production.
                                        One of the reasons why SCHOTT built the new slide production facility
                                        here in Jena was because the glass we use for our microarray substrates
                                        is manufactured on this site. This gives us total control over the quality of
          Float Glass Production        glass we use for our microarray substrates. Large sheets of glass are
                                        brought in from the production unit next door. We then carry the initial
                                        processing in a “grey room” environment.
                                        The pre-cleaned glass is laser cut into microscope slide size or other
                                        formats. The laser cutting process is a technology developed by
                                        SCHOTT, and is a major advantage from a production point of view as
                                        the cut glass has perfect edges that do not require any further finishing.
                                        In addition, the cutting process does not produce particles or micro frac-
                                        tures that might cause us problems later. After cutting the glass under-
                                        goes a “pre-quality” check to ensure that there are no scratches or de-
                                        fects in the glass.
                                        If the slides are going to have bar codes, we apply a laser bonded bar
                                        code to the glass at this stage. This is a very flexible system, and for
                                        some customers we produce custom logos or dedicated bar codes such
                                        as two-dimensional barcodes. For the new HiSens slides we apply the
             Glass Cleaning             optical coating at this stage prior to applying the functional coating. If
                                        required, we can also add the MTP / MPX pattering to the substrates at
                                        this point.
                                        The next step is a glass cleaning process done under class 100 clean
                                        room condition; at this point we either pack the cleaned uncoated slides
                                        for sale to our customers or go on to apply the functional chemistry coat-
                                        ings. In our Jena plant, we have the option of five different coating meth-
                                        ods. The facility has been designed to enable us to produce large slide
Microarray Solutions                                                                                          page 11



                                          batches, but is flexible enough to process other substrate formats such
                                          as the microplate.
                                          After the cleaning the slides have to pass a three-stage quality control
                                          1. 100% inspection of all slides by an automated camera based detector
                                          system. This system checks the geometrical properties and the homo-
                                          geneity of the glass. It also detects if there are any scratches or particles.
                                          2. We analyze the coated surface by measuring the contact angle and
                                          the background signal.
                                          3. We put a representative number of slides from each batch through a
                                          real wet lab “biological” experiment to ensure they perform as they
                                          should.
                                          The last stage is Packaging.
                                          The substrates are packaged in specially designed boxes under inert
                                          condition and in a light proof pouch. Then we apply label with product
                                          information and expiry dates. We have a production planning system that
                                          allows us to hold enough stock to meet our expected customer demand.
                                          Q: What are the most challenging aspects of producing high quality
         Quality Control                  microarray slides?
                                          We want to produce slides that are totally consistent batch to batch and
                                          that arrive at our customers’ sites in perfect condition. The slide produc-
                                          tion process has many complex steps all of which have to be tightly con-
                                          trolled. In addition, we have to take into account shipping conditions
                                          when we design our packaging.
                                          Q: How does SCHOTT assure that costumers get the highest quality
                                          microarray products?
                                          We have developed an extensive quality assurance system. Every batch
                                          of slides is supplied with a quality certificate. We expect to have DIN EN
                                          ISO 9001 certification by the end of March 2006. The next step will be
                                          DIN EN ISO 13485, a quality management certification for medical de-
                                          vices equivalent to GMP. We have a growing number of industrial slide
                                          customers who demand very high quality standards.
           Name: Christian Jabschin-      Q: What key skills are required to do your job?
           sky
           Location: Jena
                                          As we say in German a “gutes Rückgrat” - a good backbone because I
           Job Details SCHOTT
                                          have demands from all quarters. I manage a team of twelve people with
                     ®
           Nexterion Production
                                          different skill levels, so I have to be a good diplomat. I have to be multi-
           Director                       skilled in my job, as I have to know about many different subjects: surface
           Personal facts: Married        chemistry, glass technology, molecular biology and mechanical engineer-
           with 2 daughters (who keep     ing.
           him well occupied!)            Q: What part of the job do you find most satisfying?
           Outside work interests:
                                          I enjoy having new challenges each day, it keep things interesting. It is
           Sports especially hand ball,   good to work in an environment with a lot of knowledgeable people who
           fine malt whisky, and ad-
           venture traveling              are all pulling together in the same direction to produce a high quality
                                          product. I really like it when we get positive feedback from our customers
                                          about how much they like using our products.
                                          Q: What would you say were the unique features of the Nexterion®
                                          microarray slides?
                                          I am most proud of our Epoxy coated slides; tests have shown that our
                                          Slide E is the most stable and reproducible epoxy coated slide. The next
                                          thing is our glass. Being part of SCHOTT we are able to select the best
                                          glass for our products. The borofloat glass has excellent physical and
                                          chemistry properties. We are very excited about the potential of our new
                                          HiSens optical coating, and I think it gives us an edge over our competi-
                                          tors.
                                          Q: How has the range of functional slide coatings changed over the
                                          years?
                                          Although the DNA microarray slide market is still growing we are seeing a
                                          much higher customer demand for surfaces designed for protein arraying.
                                          Q: What new projects have you worked on recently?
                                          I have been heavily involved in the MTP microplate and HiSens project
                                          stabilizing the production process and starting to ramp up production.
page 12                                                                         Microarray Solutions


                        Conference and Exhibition Calendar 2005/06


                                       AMT is probably the leading European event in the microarray
                                       field. More than 200 attendees and 17 exhibitors attended AMT
  Event: Advances in Microarray        2005 to discover the latest developments in microarray tech-
  Technology (AMT 2005)                nology. SCHOTT Nexterion® presented a talk entitled “Future
  Location: London                     developments in microarray glass slides technology”.
  Date: 11 - 13 October 2005           Please contact us at coatedsubstrates@us.schott.com if you
                                       would like a pdf copy of the presentation.


                                       The protein and microplate array workshop jointly presented by
                                       SCHOTT, Genomic solutions and Alpha Innotech was well re-
  Event: Plant and Animal genome       ceived. If you would like a copy of the “Protein Microarrays:
  Location: San Diego, CA              Approaches to Printing” presentation by Dr Steven Suchyta
  Date: 17 January 2006                Applications Scientist at Genomic Solutions Inc. please contact
                                       us at coatedsubstrates@us.schott.com.


  Event: Lab Automation 2006           SCHOTT Nexterion® officially launched the Nexterion® MTP 96
  Location: Palm Springs Conven-       microplate and the Nexterion HiSens reflective slides at Lab
  tion Center Palm Springs, Califor-   Automation 2006, generating a huge amount of delegate inter-
  nia                                  est.
  Date: 21 - 25 January 2006
  Event: Statusseminar Chiptechno-     The event was very well attended with over 200 delegates
  logien,                              mainly from Germany.
  Location: Dechema Frankfurt          Details of the programme:
  Date: 2- 3 Feb 2006                  www.events.dechema.de/Programm-page-82728.html
                                       Exhibition and showcase together with OPERON
                                       If you would like a copy of the “Nexterion® HiSens Slides: A
  Event: Genomes to Systems
                                       Cure for the Sensitivity Blues – Achieve Higher Signals
  Conference 2006
                                       with Less Target” presentation by Dr Oliver Kirchner Applica-
  Location: Manchester, UK
                                       tions Scientist at SCHOTT Nexterion please contact us at
  Date: 22 - 24 Mar 2006
                                       coatedsubstrates@us.schott.com.
                                       Details of the programme: www.genomestosystems.org
  Event: WC on Microarray
  Technology 2006
                                       www.worldmicroarraycongress.org/
  Location: Vancouver / CA
  Date: 24 – 25 Mar 2006
  Event: AACR Annual Meeting
  2006
                                       www.aacr.org/page5701.aspx
  Location: Washington, DC / USA
  Date: 01 – 05 Apr 2006
  Event: 4th Symposium of The
  Wellcome Trust Funded Multi-
  Collaborative Microbial Pathogen
  Microarray Facility (BµG@S)
                                       www.ugs.sgul.ac.uk/conference
  Location: Wellcome Trust Con-
  ference Centre, Hinxton, Cam-
  bridge UK
  Date: 24 - 26 May 2006
  Event: Chips to Hits
  Location: Boston/USA                 www.chipstohits.com
  Date: 25 -28 September 2006
Microarray Solutions                                                                page 13



                       Contact



                       Fore more information about our complete product range please contact
                       us or visit our hompage.

                       www.schott.us.com/nexterion


                       Microarray Solutions
                       SCHOTT North America Inc.
                       5530 Shepherdsville Road
                       Louisville, KY 40228
                       USA
                       Phone:       +1- 502-657-4417
                       Fax:         +1- 502-966-4976
                       E-Mail:      coatedsubstrate@us.schott.com
                       Webshop: www.us.schott.com/nexterion/shop

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Microarray Solutions newsletter #1

  • 1. Microarray Solutions The SCHOTT Nexterion® Newsletter N° 1 March 2006 Page 2 to our first issue of the “Microarray Solutions” newsletter, designed to keep members of the life sci- Welcome Foreword by Dr. Lutz Wehmeier (General Manager) ences community informed history developments at SCHOTT Nexterion® and to highlight some of the interesting Short about of SCHOTT Nexterion® microarray applications that our products are currently being used for. Page 3 Nexterion® HiSens Slides “Signal and sensitivity enhancement through an optical interference coating for DNA and protein microarray applications” is the title of new scientific paper written by Dr. Rajendra Redkar, R&D Scientist at SCHOTT Nexterion® in Duryea, PA. “Microarray Solutions” gives you an insight into some of the key elements behind this pa- per and explains why users are reporting up to an 8x increase in signal intensity over regular slides with the new HiSens slides from SCHOTT Nexterion®. Page 4 Ambion HiSens E evaluation produces “incredible” results A report on Ambion's recent evaluation of Nexterion HiSens E slides with its miRNA probe set in which it saw an average 8 fold increase in signal intensity over regular glass slides, leading the company to declare that SCHOTT "has developed another premier microarray substrate." Page 5 Microplates for arraying Ever thought about using the microtiter plate format for high throughput arraying? Are you unhappy about the performance of 96 well polymeric and glass bottom plates on the market? Not sure if your arrayer is capable of arraying into plates or need advice on suitable microplate scanners? Alistair Rees (International Product Manager for Coated Substrates) discusses the new Nexterion® MTP 96 microplate and highlights some of the compatible arrayers and scan- ners available on the market. Page 7 New Product Developments • New Surfaces for Protein and Glycan Microarrays • New and Improved Slide Storage Boxes for Microarray Slides Page 8 Technical Support in Focus Having problems with signal intensity and or too high background? Interested in increas- ing spot size or improving spot morphology? Looking at ways to reduce the number of protocol steps? SCHOTT Nexterion® prides itself on offering the best technical support to customers and starting in the next edition, “Microarray Solutions” will bring you a section focusing on the most interesting trouble shooting issues addressed by our technical sup- port team and a Q&A section dedicated to tech support questions received from our read- ers. Page 9 In October 2004, SCHOTT Nexterion® opened what it considers to be the most mod- ern and hi-tech microarray slide production facility in the world. Production Director Christian Jabschinsky gives you an overview of the challenges SCHOTT faces to produce the highest quality microarray substrates and gives you a be- hind the scenes insight into how this multi-million dollar facility operates. Page 11 Conference and Exhibition Calendar 2005/06
  • 2. page 2 Microarray Solutions Foreword SCHOTT Nexterion® has come a long way since our formation back in October 2002. For those of you who are not familiar with our story, here is a brief overview of the changes that have occurred at Nexterion® over the past few years. The SCHOTT Nexterion® unit was created as a result of the Vision 2010 project during which the SCHOTT unit identified poten- tial new market segments that had high growth potential. Nexterion® Slide A, one of the Aminosilane coated slides in our portfolio, was the first product to be launched by the company in 2002. I joined the company soon after as General Manager in 2003 having spent several years run- ning the microarray business at MWG Biotech. We spent the next few months working hard to integrate the microarray slide business that had been acquired from Quantifoil, which resulted in the addition of several new surface chemistries and reagents being added to our portfolio. Just 12 months later saw the completion of our new multi-million Euro slide production facility in Jena, where all Nexterion® products are now manu- factured using modern, state-of-the-art technology. We also relocated the Nexterion® business unit from the SCHOTT corporate headquarters in Mainz to SCHOTT Jenaer Glas in Jena. Jena is an award-winning bio- technology hotspot in Germany offering Nexterion® potential synergies with other biotech companies, as well as close links with the life science driven academic community, making it an ideal location for our microar- ray business. Nexterion® has grown rapidly since 2002 and we are now proud to offer the broadest range of high quality substrates for DNA and protein arrays, both in a slide a microplate format. We have the privilege of supplying microarray consumables to some of the most important microarraying Dr. Lutz Wehmeier sites in the world and our aim to introduce exciting and innovative General Manager SCHOTT Nexterion® products into the microarray substrate market resulted this year in the launch of the MTP 96 microplate array format, a natural progression from our Multiplex (MPX) 16 and 48-well formats, and our new signal enhancing slide coating called HiSens. We have very high expectations for both products and will continue to strive to offer our customers the most innovative, forward-thinking microarray consumables. During 2005, SCHOTT Nexterion also entered into a number of collaborations with high-profile life sciences companies in the US and Europe and this is set to continue in 2006. A co-marketing agreement with Operon was signed in 2005 and resulted in the launch of a kit of slides and processing reagents optimized around the Operon 70 mer oligonucleotides. We also recently finalized a co-marketing agreement with Genomic Solutions and Alpha Innotech to promote arraying into microplates and will be organizing joint workshops with these two companies later this year. Several other important collaborations have been established behind the scenes, some of which will be announced before the end of the year, and these relationships clearly demonstrate the outstanding reputation SCHOTT Nexterion is developing throughout the world for microarray substrates and consumables. We are excited about the future of SCHOTT Nexterion®, and hope that you will enjoy future issues of this e-newsletter as we update you on fur- SCHOTT JENAer GLAS GmbH ther developments. In this edition of “Microarray Solutions”, you will find articles on our new range of HiSens and MTP products, plus some inter- esting information about our state-of-the-art production facility in Jena. We have also included a feature on Ambion and their miRNA probe sets and how HiSens slides have really changed the way of thinking at Am- bion. If you have suggestions about ways to make these updates more effective or articles you would like to see, please feel free to contact Karola at karola.koban@schott.com. Regards, Dr. Lutz Wehmeier
  • 3. Microarray Solutions page 3 Nexterion® HiSens Slides Limitations of Regular Slides for Certain Applications Microarray technology has been accepted as a preferred gene expres- sion tool in basic science research such as genotyping, metabolic path- ways, cancer research, toxicology, and functional genomics. Because this technology utilizes thousands of DNA/antibody probes representing the genome or proteome, it can be used for simultaneous detection and identification of organisms as it offers several important advantages over “Signal and sensitivity en- the standard PCR and ELISA-based detection methods. However, mi- hancement through an optical croarray technology has struggled to its logical progression into the diag- interference coating for DNA nostic field due to a lack of standardization. One such problem is the lack and protein microarray appli- of sensitivity of the microarray data, making it difficult to separate the cations” is the title of new experimentally induced variation from the true biological results. In many scientific paper written by Dr. instances the amount of RNA is limiting and the activity of low expressing Rajendra Redkar, R&D Scien- genes such as regulatory transcription factors may not be clearly quanti- tist at SCHOTT Nexterion® in fiable. Alternative labeling systems, signal amplification methods and Duryea, PA. detection technologies have all been developed in an attempt to increase the microarray sensitivity. However these alternatives are not cost- “Microarray Solutions” gives you effective and/or require cumbersome procedures, often deviating away an insight into some of the key from standard protocols that researchers are comfortable with. The new elements behind this paper and HiSens slides from SCHOTT Nexterion® offer a cost-effective solution to explains why users are reporting the sensitivity issue and are compatible with routinely used microarray up to an 8x increase in signal equipment and protocols, which coupled with higher detection sensitivity intensity over regular slides with could be critical in developing diagnostic assays. the new HiSens slides from SCHOTT Nexterion®. Optical Interference Coating to Increase Signal Intensity The optical interference coating deposited on the HiSens slides is com- prised of a multi-layered, dielectric, thin-film interference coating. The optical interference coating was carefully optimized to yield a product with consistent quality that could easily be integrated into SCHOTT Nexte- rion®’s large-scale production facility in Jena. Several specific production steps were developed to maintain the integrity of the optical interference coatings. Briefly, the thin-film dielectric coating works on the phenomenon of optical interference, which can be either constructive or destructive. By design, the interference is made constructive to enhance the photoab- sorption of the Cy3 and Cy5 dyes at the surface or in the vicinity of the surface (within ~60 nm from of the substrate), and also to reflect and redirect the microarray fluorescence signals toward the detector during scanning. The HiSens slide, therefore, differs from slides with metallic coatings that are currently on the market where the signal is only en- hanced due to reflection. Validation experiments with HiSens slides have shown a greater than eight-fold signal amplification in both Cy3 and Cy5 channels, thus provid- ing an order of magnitude increase in signal intensity. This leads to sig- nificantly higher signal-to-noise ratios in microarray experiments. Any Nexterion® HiSens Slides functional coating (Epoxysilane, Aminosilane etc.) can be applied on top of the optical interference coating for subsequent biomolecular attach- ment and consequently the HiSens slides can be used in place of tradi- tional slides without any protocol modifications. The HiSens slides have been tested using contact and non-contact microarray printers, as well as laser and CCD-based scanners, and have proven to be fully compatible with most commercially available microarray equipment. HiSens for Different Applications According to Alistair Rees, International Product Manager for Coated Slides, a wide range of applications are likely to benefit from the use of the HiSens slides. For example, applications in which researchers have only a limited amount of target material, or in which amplification of mate-
  • 4. page 4 Microarray Solutions rial is difficult or problematic. The latter includes measurement of biopsy samples and miRNA (see Ambion article below), as well as gene expres- sion monitoring and diagnostics involving weak signals. SCHOTT Nexterion® officially launched the Nexterion® HiSens slides in January with the Nexterion® Slide A (Aminosilane) and Nexterion® Slide E (Epoxysilane) functional coatings. HiSens slides will be available with other Nexterion® surface chemistries in the near future. Dr. Rajendra Redkar's paper "Signal and sensitivity enhancement through optical interference coating for DNA and protein microarray applications" can be seen in full at the citation Journal of Biomolecular Techniques 17(2): 122-130 (2006). Ambion HiSens study produces “incredible” results Ambion’s mirVana miRNA Probe Set is a collection of amine-modified DNA oligonucleotides targeting a comprehensive selection of human, mouse, and rat miRNAs from miRBase. Developed in conjunction with “HiSens E provided incredible the mirVana™miRNA Labeling Kit, the mirVana miRNA Probe Set is de- signal and high signal-to-noise, signed for preparation of “miRNA arrays” on glass slides. Previously even with significantly lower tar- Ambion, Inc. had used the Nexterion® Slide E epoxy slides to produce the get concentration… and provided miRNA arrays with great success. Ambion’s familiarity with the Slide E an average of 8 fold increase in surface chemistry made them the perfect candidate to test the new signal intensity (over regular HiSens E slides and Jeffrey Shelton in the R&D Division at Ambion was slides)” – Jeffrey Shelton of Am- sent some of the very first HiSens slides produced by SCHOTT to evalu- bion, Inc. ate. In the evaluation, the mirVana miRNA probes were printed onto 25 SCHOTT Nexterion® Slide E slides and 25 HiSens Slide E slides on the same print run. The miRNA fraction from 20 µg, 5 µg, and 2 µg of RNA from human bladder and lung were labeled using the mirVana™ miRNA Labeling Kit, and fluorescent dyes were attached using standard coupling procedures. The fluorescently labeled bladder and lung miRNA were mixed and hybridized on duplicate arrays for each substrate type. Slide E vs HiSens E 20 ug eq bladder “The HiSens slides provided an average of 8 fold increase in signal inten- vs lung miRNA tested by Ambion sity for each starting mass equivalent, with no detectable loss of signal to noise ratios. The signal I obtained from the 2µg equivalents was much greater than I had ever seen for that starting mass amount. I normally Nexterion® had to use greater than 20µg equivalents to obtain an equivalent signal Slide E on the Slide E or similar substrates,” Jeffrey Shelton reported. Shelton went on to say, “The amine-modification of the mirVana miRNA probes makes them ideally suited for use with epoxy or aldehyde surface chemistries. We have recommended SCHOTT Nexterion® Slide E mi- croarray slides as they are convenient, easy to use, and provide consis- Nexterion® tent results. However, since this evaluation, it is our intention to recom- HiSens E mend the Nexterion® HiSens E to customers who wish to maximize the signal from small starting mass RNA fractions. With HiSens E, SCHOTT Nexterion® has developed another premier microarray substrate.” Although other microarray slides claiming to enhance signal intensity have appeared on the market in the past, with some still commercially available today, this type of slide has failed on the whole to take off with users typically complaining of poor slide reproducibility, long lead times to get hold of the slides and usually a very high price. “I have tried other manufacturers’ reflective substrate slides in the past and was not at all impressed”, continued Shelton. “I went into this beta test of HiSens E somewhat skeptical, but now I’m your newest customer! The HiSens E slides provided incredible signal, high signal-to-noise, and no significant increase in background.”
  • 5. Microarray Solutions page 5 The results of the HiSens evaluation carried out by Ambion clearly dem- onstrate that HiSens slides could be an invaluable tool for applications in which researchers have only a limited amount of target material, or in For further information on Ambion, which amplification of material is difficult or problematic. This is particu- Inc. and its range of products, in- larly the case for miRNA microarrays because the miRNA is only a minor cluding the mirVana miRNA Probe part of the whole RNA fraction (around 1/10000), but HiSens could also Set, please visit the Ambion web- be a useful tool for biopsy samples, as well as gene expression monitor- site at www.ambion.com ing and diagnostics involving weak signals. Many signal amplification techniques have been developed in recent years to combat this problem but most of these techniques raise questions about biased amplification that could ultimately affect the quality of the experimental results. With Nexterion® HiSens slides, these concerns are eliminated and Ambion is likely to be the first of many customers to benefit from this exciting new technology from SCHOTT Nexterion. Microplates for arraying Although the microtiter plate format has been a standard research tool for clinical diagnostics and drug discovery for some time, it still has not be- Ever thought about using the come a popular microarray tool despite the recent introduction of high- microtiter plate format for high resolution plate scanners and compatible arrayers. Feedback from the throughput arraying, but un- market, however, seems to indicate that this technology may finally be happy about the 96 well poly- coming to the fore and many companies are now actively looking to intro- meric and glass bottom plates duce products that will allow users to pursue high-throughput microarray- on the market? Not sure if your ing with the microtiter plate format. arrayer is capable of arraying into plates or need advice on SCHOTT’s new 96-well glass bottom microtiterplates are the result of two suitable microplate scanners? years of development work at one of SCHOTT Nexterion®’s R&D Centers of Excellence in Duryea, PA and were developed in response to market Alistair Rees (International Prod- demand, which indicated that there were numerous limitations with con- uct Manager for Coated Sub- ventional 96 well polymeric and existing glass bottom microtiter plates strates) discusses the new Nex- utilized in microarraying. terion® MTP 96 microplate and highlights some of the compatible Some of the weaknesses identified in these existing products included: arrayers and scanners on the • Printable area per well: microarray print heads cannot access the market. entire well plate area because the wells are recessed, thus limiting the number of features per well and arrayer compatibility. • Print time: the depth of the wells, and the subsequent additional Z- axis travel, makes printing time consuming. • Well contamination: the intra-well print area may be restricted due to the contamination of the well edges with bonding adhesive. In addi- tion, adhesive out-gassing can affect functional coating performance. • Coating range & uniformity: difficulty in uniformly applying functional coatings to three dimensional polymeric microtiter plates. • Plate flatness: conventional microtiter plates suffer from poor optical transparence and flatness. In collaboration with a high-profile biotech company in the San Francisco Bay Area, and in consultation with several customers in Europe and the US, SCHOTT Nexterion® took up the challenge of designing a product that eliminated the key weaknesses outlined above and offered its own unique characteristics to assist customers. Dan Haines, Advanced Mate- Nexterion® Microtiterplate Kit rials & Coatings Research Scientist at Schott North America in Duryea, PA and head of the team that designed the Nexterion® MTP microarray products, is extremely satisfied with the final product design. “We are excited to provide a new research platform that combines our high quality coatings with an innovative 96-well microtiter plate design that makes the transition from (multiplexed) microscope slides to microtiter plates seam- less. The low-fluorescent glass plate can be printed/processed/scanned without it ever being removed from its tray for those users desiring high
  • 6. page 6 Microarray Solutions throughput – alternatively, the plate can be quickly and easily re- ® moved/inserted depending on the experimental protocols and equipment Nexterion MTP 96 Microtiterplate Kit consists of three main available to the researcher. Well contamination problems are resolved by components use of a recessed adhesive on the superstructure that preferentially binds to the hydrophobic patterning material. The removable superstructure allows for unencumbered full area printing of the wells while allowing hybridization and wash volumes up to 200 µl/well. This platform has been validated both by our customers and equipment partners Alpha Innotech and Genomic Solutions. For a researcher desiring higher ex- perimental throughput while maintaining current slide-based protocols and procedures, the Nexterion® MTP platform provides a flexible tool.” Glass Plate Nexterion® MTP 96 consists of three main components: a microarray quality patterned glass substrate, a 96-well silicone superstructure and a microtiter plate tray support. It is available as a complete kit or as sepa- rate components, with the glass substrates offered with either the Slide E (Epoxy) or Slide A (Aminosilane) functional coatings or as uncoated glass for custom applications. The Nexterion® MTP 96 design fully conforms to SBS (Society for Biomolecular Screening) standards and is suitable for high-throughput robotic handling. One of the major benefits of the Nexte- Superstructure rion® MTP 96 plate is that the design of the kit components allows the plate to be used in any make of microplate arrayer. Over 1000 spots can be printed into each of the 96 wells due to the larger effective well area (49mm2) and printing time is significantly reduced as the printing pins are subject to less Z axis travel compared to conventional 96 well microtiter plates. Microplate Array Printers Modern robotic arrayers, both contact and non-contact, are already equipped to handle the 96-well format and many have pre-programmed Tray, lid, fixing pins definitions for the Nexterion® MTP 96 plates, thus simplifying set up. and sealing film However it may be necessary to purchase additional array control soft- ware and a replacement arraying bed to hold the microplates during print- ing. The following table details arrayers can be modified to array into mi- croplates: Arrayer Deposition Destination method microplate Arrayjet AJ120 Non-contact 20 Aushon Biosystems 2470 Contact 20 Bio-Rad BioOdyssey Calligrapher Contact 2 Bio-Rad VersArray ChipWriter Pro Non-contact 1 GeneMachines OmniGrid Accent Contact 6 Genetix QArray2 Contact 16 Genetix QArray mini Contact 4 Genomic solutions MicroGrid Contact 16 Lab Next Xact Contact 2 Lab Next THOMAS™ Contact 9 PerkinElmer Piezorray Non-contact 5 Scienion sciFLEXARRAYER Non-contact 4 Telechem NanoPrint™ Contact 12 The Genomic Solutions arrayers have defined parameters for the Nexte- rion® MTP 96 microplates in the plate arraying software. A software up- grade is available from Genomic Solutions to accommodate the switch from slides to Nexterion® MTP 96 for the OmniGrid Accent model.
  • 7. Microarray Solutions page 7 Microplate Scanners Arguably the biggest obstacle to the wider use of microplate arrays has been the lack of access to microplate compatible high-resolution scan- ners. A number of suitable scanners are now commercially available and the following table details some of the scanners that are compatible with the Nexterion® MTP 96 microplate: Manufacturer Model Alpha Innotech Corporation NovaRay® Detection Platform Blueshift Biotechnologies, Inc IsoCyte™ laser scanning fluorimeter TECAN Laser Scanner The Alpha Innotech NovaRay® Detection Platform is compatible with both slides and microplates and offers multi-spectral imaging with eight emis- sion wavelengths. A less well-known system is the IsoCyte™ Benchtop NEXTERION NEWSFLASH! Laser Scanner from Blueshift Biotechnologies in Sunnyvale, CA. The scanner was developed for high throughput analysis of array-, bead- or US Government Awards SCHOTT $1M to Develop Microarray Platform for live cell-based assays in microplates and on slides and the company Pathogen Detection claims that the system can scan a microplate such as Nexterion® MTP 96 is less than two minutes. According to Blueshift Biotechnologies, the sys- The US government has allotted $1 tem accomplishes this task by fast “object” characterization (e.g. spots or million of its defense appropriations bill to Schott North America to develop a mi- cells) and unique imaging in the fluorescence polarization domain. croarray-based platform for detecting biological agents, Schott said recently. SCHOTT Nexterion® recently partnered with Genomic Solutions and According to Duryea, Penn.-based Schott Alpha Innotech at the Plant & Animal Genome Conference in San Diego, NA, the funding was secured through the CA to demonstrate the ease of use and flexibility offered by the Nexte- offices of Congressman Paul Kanjorksi rion® MTP 96 system and its compatibility with the Genomic Solutions (D-Penn.). Schott will collaborate with the MicroGrid and OmniGrid arrayers and the NovaRay® Detection Platform University of Scranton's Institute of Mo- lecular Biology and Medicine to develop from Alpha Innotech. Jeremy Clarke, Global Product Manager at Ge- the fully automated and multiplexed nomic Solutions, was impressed by the level of interest shown at the microarray platform, the company said. conference and clearly feels that the MTP format is now seriously being considered as a suitable tool for high-throughput microarraying. “The The new platform would be a 96-well microarray, with the potential to screen presentation was well attended and significant interest in the products for up to 2,000 pathogens in each well, from all three companies was registered by attendees, both during and Schott said. after the event, suggesting that the microtiter plate format is finally being considered by researchers as a serious microarray tool for the near fu- ture”, Clarke told “Microarray Solutions”. All three companies are commit- ted to continuing this relationship in an effort to promote microplates and three further workshops are planned for the US in May in San Francisco, CA, Houston, TX and Boston, MA. Clarke went on to say, “We are look- ing forward to continuing our relationship with SCHOTT Nexterion® and Alpha Innotech. Together, we offer a range of complementary products which provide the best solution for fulfilling the new protein arraying work- flow”. Details of the forthcoming workshops with Genomic Solutions and Alpha Innotech will be available soon, including an agenda and list of invited speakers for the three locations. Please contact Karola at coatedsub- strate@schott.com for further information.
  • 8. page 8 Microarray Solutions New Product Developments SCHOTT Nexterion® to Develop New Surfaces for Protein and Gly- can Microarrays In consultation with customers and collaborators, SCHOTT Nexterion® has identified protein and glycan microarrays as promising applications with large growth potential for the future. The feedback that we have re- ceived from the market so far indicates that one of the biggest challenges facing customers is the directed immobilization of probe molecules and SCHOTT Nexterion® is now focusing some of its R&D efforts on identify- ing suitable surfaces to resolve this issue. We are also looking to expand our product portfolio by offering additional surfaces for direct immobilization of different probe molecules, for exam- ple His-tag, maltose binding protein or lectin coatings. We are very inter- ested in getting feedback from customers on what type of surfaces they would like to see offered by SCHOTT Nexterion® in the future. Please feel free to send your suggestions to us and one of our R&D team mem- bers will contact you to discuss your ideas in greater detail. Please sub- mit your ideas to coatedsubstrate@schott.com and help develop the next generation microarray slide surfaces! SCHOTT Nexterion® Announces New and Improved Slide Storage Boxes for Microarray Slides SCHOTT Nexterion® has introduced a new 25-slide storage box for its microarray slides which will replace the current 5-slide mailers used for Nexterion® Slide A+ and AL. This new rigid slide box does not shed plas- tic particles or outgas plasticizer and allows SCHOTT Nexterion® to send the products in 25-slide storage boxes. Unique design features include tabs that are moulded into the lid to prevent the glass substrates from moving, thus reducing the risk of breakage during transportation, and a New Nexterion® 25-slide storage box new hinge lid with a catch which prevents accidental opening of the stor- age box.
  • 9. Microarray Solutions page 9 Technical Support in Focus Name: Ruediger Dietrich Having problems with signal intensity and or too high background? Inter- Location: Jena ested in increasing spot size or improving spot morphology? Looking at Job Details: Director R&D ways to avoid certain protocol steps? SCHOTT Nexterion® prides itself on and Tech Support offering the best technical support to customers. That’s why we will bring Likes: good food you a section with the most interesting troubleshooting issues addressed Dislikes: bad food by our technical support team starting in next edition of “Microarray Solu- Interests: hiking, skiing, tions”. In addition, we planned to include a Q&A section dedicated to tech kayaking, preparation of support questions received from our readers. food like cheese, marinated herrings, sauerkraut etc. Meet Nexterion’s Technical Support Team - Dr. Ruediger Dietrich, Direc- tor of R&D at the SCHOTT Nexterion HQ in Jena, Germany and Mike Wotring, R&D Scientist at one of SCHOTT’s R&D Centers of Excellence in Duryea, PA. As Nexterion’s Technical Support Specialists, Ruediger and Mike are involved with all technical aspects of our product line - from new product development to protocol optimization, as well as ongoing Name: Mike Wotring customer application support. Location: Duryea Job Details R&D Scientist Ruediger and Mike have been active in responding to numerous requests Likes: Travel for technical support from customers all over the world. Future editions of Dislikes: There's never “Microarray Solutions” will feature some of the most interesting trouble- enough time to see every- shooting issues addressed by Ruediger and Mike, including case studies thing! demonstrating how they responded to a specific customer application Interests: Reading, cook- ing, hiking, kayaking issue and were able to help the customer obtain better results. The new “Technical Support in Focus” section will also allow you to submit your technical questions to Ruediger and Mike, some of which we will feature in future editions of “Microarray Solutions”. Do you have a protocol problem or need help optimizing your microarray application? Please submit your question to: coatedsubstrate@us.schott.com Your question may be featured in future editions of the “Microarray Solu- tions”.
  • 10. page 10 Microarray Solutions State of the art Microarray Substrate Production Facility Q: How long have you worked for SCHOTT? And where do you work prior to SCHOTT? I have worked for SCHOTT since September 2003. I transferred when SCHOTT acquired the microarray business from Quantifoil Micro Tools In October 2004, SCHOTT Nex- who were also based in Jena (Germany). I originally joined Quantifoil just terion opened what it consid- as they started their microarray slide business in May 1999, so I have ers to be the most modern and many years experience in microarray slide production! Prior to Quantifoil, hi-tech microarray slide pro- I studied medical engineering at the University of Applied Science in duction facility in the world. Jena. Q: How long has SCHOTT been producing microarray substrates? Production Director Christian SCHOTT originally developed and started to manufacture the first Nexte- Jabschinsky gives you an over- rion® microarray product, our Aminosilane coated Slide A, at Duryea in view of the challenges SCHOTT Pennsylvania back in October 2002. At SCHOTT in Jena, we have been faces to produce the highest producing coated slides since October 2004, when we commissioned the quality microarray substrates and new substrate production facility. Virtually all the personal involved in the gives you a behind-the-scenes Quantifoil microarray slide business transferred to SCHOTT when they insight into how this multi-million acquired us. This means that we have microarray slide development and dollar facility operates. production expertise that goes back over seven years. Q: Why is Jena a good location for SCHOTT's biotech business? The tradition for scientific based enterprises in Jena goes back to Carl Zeiss, when in 1846 he created his first workshop here. Much more re- cently in 1996, the BioRegio network Jena won the German BioRegio competition with its "bio instrument Jena" concept. The network consists of established companies like Carl Zeiss and SCHOTT and the younger companies like Jenoptik, together with over 31 start up companies many spun off from the University. In addition, there are several major aca- demic institutes in Jena also involved in the network. We have benefited from our close cooperation with the University, in particular the Institute of surface coating, as we have many students on placement working at SCHOTT. Q: Can you summarize the production process in your facility? The first step is glass production. One of the reasons why SCHOTT built the new slide production facility here in Jena was because the glass we use for our microarray substrates is manufactured on this site. This gives us total control over the quality of Float Glass Production glass we use for our microarray substrates. Large sheets of glass are brought in from the production unit next door. We then carry the initial processing in a “grey room” environment. The pre-cleaned glass is laser cut into microscope slide size or other formats. The laser cutting process is a technology developed by SCHOTT, and is a major advantage from a production point of view as the cut glass has perfect edges that do not require any further finishing. In addition, the cutting process does not produce particles or micro frac- tures that might cause us problems later. After cutting the glass under- goes a “pre-quality” check to ensure that there are no scratches or de- fects in the glass. If the slides are going to have bar codes, we apply a laser bonded bar code to the glass at this stage. This is a very flexible system, and for some customers we produce custom logos or dedicated bar codes such as two-dimensional barcodes. For the new HiSens slides we apply the Glass Cleaning optical coating at this stage prior to applying the functional coating. If required, we can also add the MTP / MPX pattering to the substrates at this point. The next step is a glass cleaning process done under class 100 clean room condition; at this point we either pack the cleaned uncoated slides for sale to our customers or go on to apply the functional chemistry coat- ings. In our Jena plant, we have the option of five different coating meth- ods. The facility has been designed to enable us to produce large slide
  • 11. Microarray Solutions page 11 batches, but is flexible enough to process other substrate formats such as the microplate. After the cleaning the slides have to pass a three-stage quality control 1. 100% inspection of all slides by an automated camera based detector system. This system checks the geometrical properties and the homo- geneity of the glass. It also detects if there are any scratches or particles. 2. We analyze the coated surface by measuring the contact angle and the background signal. 3. We put a representative number of slides from each batch through a real wet lab “biological” experiment to ensure they perform as they should. The last stage is Packaging. The substrates are packaged in specially designed boxes under inert condition and in a light proof pouch. Then we apply label with product information and expiry dates. We have a production planning system that allows us to hold enough stock to meet our expected customer demand. Q: What are the most challenging aspects of producing high quality Quality Control microarray slides? We want to produce slides that are totally consistent batch to batch and that arrive at our customers’ sites in perfect condition. The slide produc- tion process has many complex steps all of which have to be tightly con- trolled. In addition, we have to take into account shipping conditions when we design our packaging. Q: How does SCHOTT assure that costumers get the highest quality microarray products? We have developed an extensive quality assurance system. Every batch of slides is supplied with a quality certificate. We expect to have DIN EN ISO 9001 certification by the end of March 2006. The next step will be DIN EN ISO 13485, a quality management certification for medical de- vices equivalent to GMP. We have a growing number of industrial slide customers who demand very high quality standards. Name: Christian Jabschin- Q: What key skills are required to do your job? sky Location: Jena As we say in German a “gutes Rückgrat” - a good backbone because I Job Details SCHOTT have demands from all quarters. I manage a team of twelve people with ® Nexterion Production different skill levels, so I have to be a good diplomat. I have to be multi- Director skilled in my job, as I have to know about many different subjects: surface Personal facts: Married chemistry, glass technology, molecular biology and mechanical engineer- with 2 daughters (who keep ing. him well occupied!) Q: What part of the job do you find most satisfying? Outside work interests: I enjoy having new challenges each day, it keep things interesting. It is Sports especially hand ball, good to work in an environment with a lot of knowledgeable people who fine malt whisky, and ad- venture traveling are all pulling together in the same direction to produce a high quality product. I really like it when we get positive feedback from our customers about how much they like using our products. Q: What would you say were the unique features of the Nexterion® microarray slides? I am most proud of our Epoxy coated slides; tests have shown that our Slide E is the most stable and reproducible epoxy coated slide. The next thing is our glass. Being part of SCHOTT we are able to select the best glass for our products. The borofloat glass has excellent physical and chemistry properties. We are very excited about the potential of our new HiSens optical coating, and I think it gives us an edge over our competi- tors. Q: How has the range of functional slide coatings changed over the years? Although the DNA microarray slide market is still growing we are seeing a much higher customer demand for surfaces designed for protein arraying. Q: What new projects have you worked on recently? I have been heavily involved in the MTP microplate and HiSens project stabilizing the production process and starting to ramp up production.
  • 12. page 12 Microarray Solutions Conference and Exhibition Calendar 2005/06 AMT is probably the leading European event in the microarray field. More than 200 attendees and 17 exhibitors attended AMT Event: Advances in Microarray 2005 to discover the latest developments in microarray tech- Technology (AMT 2005) nology. SCHOTT Nexterion® presented a talk entitled “Future Location: London developments in microarray glass slides technology”. Date: 11 - 13 October 2005 Please contact us at coatedsubstrates@us.schott.com if you would like a pdf copy of the presentation. The protein and microplate array workshop jointly presented by SCHOTT, Genomic solutions and Alpha Innotech was well re- Event: Plant and Animal genome ceived. If you would like a copy of the “Protein Microarrays: Location: San Diego, CA Approaches to Printing” presentation by Dr Steven Suchyta Date: 17 January 2006 Applications Scientist at Genomic Solutions Inc. please contact us at coatedsubstrates@us.schott.com. Event: Lab Automation 2006 SCHOTT Nexterion® officially launched the Nexterion® MTP 96 Location: Palm Springs Conven- microplate and the Nexterion HiSens reflective slides at Lab tion Center Palm Springs, Califor- Automation 2006, generating a huge amount of delegate inter- nia est. Date: 21 - 25 January 2006 Event: Statusseminar Chiptechno- The event was very well attended with over 200 delegates logien, mainly from Germany. Location: Dechema Frankfurt Details of the programme: Date: 2- 3 Feb 2006 www.events.dechema.de/Programm-page-82728.html Exhibition and showcase together with OPERON If you would like a copy of the “Nexterion® HiSens Slides: A Event: Genomes to Systems Cure for the Sensitivity Blues – Achieve Higher Signals Conference 2006 with Less Target” presentation by Dr Oliver Kirchner Applica- Location: Manchester, UK tions Scientist at SCHOTT Nexterion please contact us at Date: 22 - 24 Mar 2006 coatedsubstrates@us.schott.com. Details of the programme: www.genomestosystems.org Event: WC on Microarray Technology 2006 www.worldmicroarraycongress.org/ Location: Vancouver / CA Date: 24 – 25 Mar 2006 Event: AACR Annual Meeting 2006 www.aacr.org/page5701.aspx Location: Washington, DC / USA Date: 01 – 05 Apr 2006 Event: 4th Symposium of The Wellcome Trust Funded Multi- Collaborative Microbial Pathogen Microarray Facility (BµG@S) www.ugs.sgul.ac.uk/conference Location: Wellcome Trust Con- ference Centre, Hinxton, Cam- bridge UK Date: 24 - 26 May 2006 Event: Chips to Hits Location: Boston/USA www.chipstohits.com Date: 25 -28 September 2006
  • 13. Microarray Solutions page 13 Contact Fore more information about our complete product range please contact us or visit our hompage. www.schott.us.com/nexterion Microarray Solutions SCHOTT North America Inc. 5530 Shepherdsville Road Louisville, KY 40228 USA Phone: +1- 502-657-4417 Fax: +1- 502-966-4976 E-Mail: coatedsubstrate@us.schott.com Webshop: www.us.schott.com/nexterion/shop