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September 26, 2002
FD10 Next-Generation DNA Microarray System
3-D Structure Chip Substrate Enables Tenfold Reduction in Reaction Time, Combined With High Sensitivity and Simple Operation
"FD10" Next-generation DNA Microarray System
"FD10" Next-generation DNA Microarray System
Olympus Optical Co., Ltd. (President: Tsuyoshi Kikukawa) is pleased to announce the launch of the FD10 next-generation DNA microarray (Note 1) system. The FD10 is based around the PamChip(R), a custom-made microarray*1, developed by PamGene. The PamChip(R) consists of a solid three-dimensional structure that facilitates the incorporation of probe molecules. It can bind hundreds more probe molecules than is feasible with conventional 2-D microarrays. The FD10 also combines (1) ease of operation, (2) a hybridization incubator that permits highly reproducible hybridization reactions within a short period of time (approx. 20mins~2hrs, more than ten times quicker*2 than existing methods), and (3) an image acquisition optical system. The FD10 will go on sale in Japan and other countries in Asia, with the principal target market comprising universities, various other academic research institutions, pharmaceutical firms, and food manufacturers.
*1:  The 3-D chip substrate can be pre-spotted with probes based on specific customer requirements.
*2:  As of September 26, 2002.
The FD10 will be exhibited at the upcoming 61st Annual Meeting of the Japanese Cancer Society (convention president: Tomoyuki Kitagawa, Director of The Cancer Institute, Japanese Foundation for Cancer Research), which is due to be held at Tokyo International Forum during October 1-3. Several Japanese academic groups with whom Olympus has been undertaking joint research in the field also plan to make presentations at the convention regarding the practical application of this microarray system to toxicity evaluations (Note 2) of chemical substances in the determination of carcinogenicity*3. These groups are led by Prof. Tomoyuki Shirai, researcher in experimental pathology and tumor biology at Nagoya City University Graduate School of Medical Sciences, Prof. Shoji Fukushima, researcher in urban environmental pathology at Osaka City University Graduate School of Medicine, and Seiko Tamano, President of the Daiyu-kai Institute of Medical Science.
*3:  Based on Japanese Cancer Society abstracts.
*  Since the microarray is custom-manufactured, the price varies according to the number and variety of the pre-spotted probes, and the quantity of units ordered. Besides microarrays with applications in gene expression profiling (Note 3), the company can also take orders for microarrays for use in gene mutation studies (Note 4) and SNP typing analyses(Note 5).
Main Features
1. Microarray analysis with high sensitivity and reproducibility
2. High-speed reactions that enable reduction of time from sample input to image acquisition by more than 90% relative to existing methods
3. Simple operation with applicability to varied, inexpensive fluorescent labels
4. Kinetic signal-detection measurements (Note 6) made possible by using image acquisition to record changes with time and temperature
5. Various analytical applications
"PamChip(R)" 3-D Chip Substrate Microarray

"PamChip(R)" 3-D Chip Substrate Microarray
Product Background
Even as DNA microarray technology has become an indispensable research tool within the life sciences, in recent years efforts to make the technology more effective have helped to boost its use in practical applications in fields such as medicine and drug discovery. In medical applications, it is being applied to diagnose disease early and to study the possible side-effect profiles of individuals to specific drugs. Such advances hold out the promise of enhanced rates of curing disease, as well as medical treatments that can actually be patient-customized. In the field of drug discovery, DNA microarray technology allows researchers to analyze the induction or suppression of gene expression by particular chemical compounds, the precise pattern of which relates to the toxicity of those compounds in the human body. Once enough results in this area have been accumulated and standardized, it will be possible to apply this knowledge to evaluate the toxicity of large numbers of compounds that are drug candidates. Ultimately this development is expected to help to vastly narrow down the number of drugs being put through animal testing for toxicity screening purposes, which would greatly reduce the time and cost involved in pharmaceutical development.

Another key factor that it is hoped will boost the effectiveness of such applications is the focused array (Note 7). Rather than employing a large-scale microarray that targets all genes identified on a genome, a focused array contains probes for a comparatively small number of genes, measured in the tens or hundreds. The use of this group effectively narrows the search to those genes specifically related to a certain disease or to the study of a certain drug's user response or toxicity profile. It is thought that such arrays will eventually not only be used in research, but also entire widespread use within the clinical testing market.

The FD10 system incorporates just such a next-generation focused DNA microarray, which is the product of a joint development program between Olympus and PamGene B.V. (Head Office: `s-Hertogenbosch, Netherlands; CEO: Tim Kievits). The PamChip(R) microarray employs a unique three-dimensional chip substrate. It also possesses a hybridization incubator, a structural feature that enables hybridization reactions to occur at optimal efficiency while simultaneously allowing rapid array image acquisition. Completely integrated with an image acquisition optical system, the FD10 not only delivers simple, fast analysis, but also boasts high data reliability and reproducibility, together with excellent sensitivity.

Olympus plans to continue to actively seek to collaborate with universities and other research institutions in the development of applications for this technology. By supporting research into gene function, the company hopes to make a significant contribution to a society where medical treatments can be patient-customized.

Details of Main Features
1. Microarray analysis with high sensitivity and reproducibility
  Use of a chip substrate with a three-dimensional structure (a multi-porous membrane, through which the sample solution can flow) facilitates the incorporation into a solid phase of hundreds more probe molecules per array spot than is feasible with conventional 2-D microarrays. In addition, the microarray contains an incubator that enables hybridization reactions to take place at high efficiency by means of a solution-driven hybridization mechanism facilitated by the multi-porous chip substrate structure. The FD10 integrates this arrangement with a CCD-based image acquisition optical system that permits rapid image acquisition. The result is a system capable of high-speed hybridization reactions at outstanding levels of sensitivity and reproducibility (detection of target nucleic acids is possible at the order of femtomoles*4, i.e. around 1.5x109 target molecules within a single 50-μl sample). Moreover, data reliability and reproducibility are considerably enhanced by the use of proprietary software that facilitates simple control of all environmental reaction parameters such as temperature and duration. Such software enables the analysis of many samples under uniform conditions.
*4. Figure for anti-sense oligo-target nucleic acids (As of September 26, 2002).

2. High-speed reactions that enable reduction of time from sample input to image acquisition by more than 90% relative to existing methods
  Capitalizing on the flow-through structure of the chip substrate, the sample solution is pumped repeatedly through the three-dimensional porous structure. This unique solution-driven hybridization system considerably boosts the efficiency of the reactions between the probes and the target nucleic acids in the sample, which in turn drastically shortens the time required from sample input to data acquisition, to less than 10% of the time typically required with conventional microarrays.

3. Simple operation with applicability to varied, inexpensive fluorescent labels
  Operation of the FD10 simply requires the fluorescent-labeled sample to be dripped onto the PamChip(R) installed in the main body of the machine FD10. It handles the process from reaction to image acquisition in a smooth, integrated flow, and analyses can be conducted continuously on the same machine. Moreover, since the optical system employed for array image acquisition is based on fluorescence microscopy optics, the sample can be labeled with diverse or inexpensive fluorescent labels.

4. Kinetic signal-detection measurements made possible by using image acquisition to record changes with time and temperature
  The combination of the hybridization incubator and the array image acquisition optical system permits kinetic signal-detection measurements to be taken, so that variations in signal strength and reaction temperature can be recorded while the hybridization reactions are proceeding.

5.

Various analytical applications
  The FD10 can be used in a wide variety of potential applications, including gene expression profiling, gene mutation studies, and SNP typing analyses.

Structure of FD10 Next-generation DNA Microarray System
Structure of FD10 Next-generation DNA Microarray System
Solution-driven Hybridization
Solution-driven Hybridization
(NOTES)
1. DNA microarray
  A DNA microarray is a sensor device for the detection and analysis of expression and mutation over large numbers of genes. It works by fixing DNA probes onto probe spots a hundred microns in diameter that are arranged on a glass slide or other substrate.

2. Toxicity evaluation of chemical substances
  This refers to the evaluation of the safety of chemical substances with respect to ecosystems, including humans.

3. Gene expression profiling
  Gene expression profiling measures the quantity and variety of numerous messenger RNAs (mRNA: the nucleic acid that transmits genetic information from DNA before its expression in proteins)

4. Gene mutation
  Gene mutation involves changes in the genetic information encoded in DNA through the substitution, insertion or deletion of portions of the affected gene's base-pair sequence, which causes the loss of the original information. Such mutation can be a factor in the genesis of diseases such as cancer.

5. SNP
  The phenomenon of Single Nucleotide Polymorphism (SNP) refers to differences of a single base pair within a genomic DNA sequence of 300-500 base pairs; the study of such differences within the human population is expected to yield genetic markers that could signal a person's susceptibility to a certain disease, or else provide clues as to the likely response to a drug and its possible side-effect profile.

6. Kinetic measurement
  Kinetic measurement of a reaction involves analysis of the nature of the variation in the speed of the reaction under various conditions, which helps to elucidate the detailed mechanism of the reaction.

7. Focused array
  A focused array is a microarray loaded with a relatively small number of DNA probes (several tens or hundreds) that contain target genes selected for specific purposes.
Main Specifications
PamChip(R) 3-D chip substrate microarray
Probe Variety/Number Made to order
Applicable Analytical Methods Gene expression profiling, gene mutation studies, SNP typing analyses
FD10 next-generation DNA microarray system
Applicable Microarray PamChip(R)
Illumination Metal halide source
Imaging Cooled CCD system
Applicable Fluorescent Labels Standard: FITC
(Cy3 and Cy5 planned options)
Temperature Control Ambient temperature range:
35 degrees - 80 degrees
Solution Control 4-channel syringe pump
Cleaning System Semi-automatic
External Dimensions
(excluding protrusions)
Main body: W621mm x H659mm x D543mm
Light source: W100mm x H125mm x D200mm
Control unit (PC):
W621mm x H459mm x D447mm
Weight Approx. 110kg (including PC)
Power/Power Consumption 100V~7.3A
50/60Hz (including PC)
Control Unit (PC) AT-compatible desktop PC
LCD monitor (17-inch, SXGA)
OS:Windows(R) 2000 SP2
Analytical software
Software Application Modules Gene expression profiling
Gene mutation studies/SNP typing analyses
Image Data Format 16-bit TIFF images
Company Information: PamGene B.V.
Chief Executive Officer : Tim Kievits
Address : Burgemeester Loeffplein 70A 5211
RX 's-Hertogenbosch, The Netherlands
Tel : +31 (0)73 615 80 80
Fax : +31 (0)73 615 80 81
URL : http://www.pamgene.com/
Business Outline : PamGene is a post-genomics biotech company, which has patented technologies for a second-generation microarray platform and an expression profiling system. Its major shareholders include GIMV, Alta Partner, Life Science Partner, and, of course, Olympus Optical, PamGene's strategic partner. The new microarray jointly developed by PamGene and Olympus delivers faster, more accurate gene analysis at lower cost. PamGene will supply this technology for a variety of purposes such as academic research, pharma and biotech R&D, and health management, as well as for non-pharma life science applications in agriculture and food production. With its extensive product lineup based on microarray core technology, PamGene is strongly committed to contributing to new pharmaceuticals development, academic research, health management, and biotechnology research.
*Olympus Optical Co., Ltd. was changed to OLYMPUS CORPORATION as of October 1, 2003.
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