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December 5, 2001
Development of a Prototype MMF Analyzer
A single molecular fluorescence detection system
that enables high-speed analysis of protein
and DNA interactions in a few seconds
--- Full-fledged Development in Genome Medical Business ---
Prototype Multiple Molecule Fluorescence (MMF) Analyzer
Prototype Multiple Molecule Fluorescence (MMF) Analyzer
* This news release is only for the Japanese market.
Olympus Optical Co., Ltd. (President: Tsuyoshi Kikukawa) has jointly developed with Evotec OAI AG (Hamburg, Germany) a prototype Multiple Molecule Fluorescence (MMF) analyzer, a single molecular fluorescence detection system that enables analysis in a few seconds at a single molecule level of the interactions between biological molecules (proteins, DNA, etc.) on a microplate. The system has applications in the field of proteome analysis (protein functionality) that has been a focus of attention. Olympus will develop the prototype system to take into account market needs for drug discovery and genomics-based research, and plans to make the commercialized analyzer available by summer 2002.
The prototype single molecular fluorescence-detecting MMF analyzer will be exhibited at the 24th Annual Meeting of THE MOLECULAR BIOLOGY SOCIETY OF JAPAN (Annual Meeting President: Prof. Masayuki Yamamoto, Graduate School of Science, University of Tokyo, Department of Biophysics and Biochemistry) held at the Pacifico Yokohama between December 9-12, 2001.
Top Features
1. Enables high-speed analysis of protein and DNA interactions, with high sensitivity and low noise.
2. Pre-analysis sample washing not necessary.
3. Solid-phased biological assay not necessary as no reliance on sensor-chips.
Development Background
It is now becoming clear that the human genome is made up of 3 billion base pairs and genomic research is moving from "structural analysis" of gene sequences to "functional analysis" of the proteins produced by the genes. An understanding of what type of behavior is exhibited by the 100,000-200,000 protein types produced by the genes in the cells, what biological molecules they interact with, and what function they have is vital for the latest genomic drug discovery and for a better elucidation of the life process.
The prototype single molecular fluorescence-detecting MMF analyzer is the first system ever to enable analysis of molecular interactions under conditions close to those found inside the cell, using a single molecular fluorescence detection method (FIMDA *1) and simultaneous measurement of numerous molecular data parameters (size, concentration, fluorescent brightness, etc.). The system can be used in a wide range of biological applications, from low molecular weight compounds (pharmaceuticals, etc.) to high molecular weight proteins and DNA. Analytical technique using cross-correlation*2 and polarization analysis are also possible.
The single molecular fluorescence detection technology built into the MMF prototype is also used in the contract analysis services provided by the Olympus's subsidiary NovusGene Inc. (President: Dr. Toshio Sofuni; Hachioji City, Tokyo). The high reliability of the data from the system has already been demonstrated. The main types of service and R&D activities in which NovusGene plans to be involved are as follows:
Main features
1. Enables high-speed analysis of protein and DNA interactions, with high sensitivity and low noise.
The system enables noise reduction and highly sensitive measurement of the fluorescent signal (over 0.1 nM/L) through the use of a confocal microscopy and a highly sensitive fluorescence detection device (Avalanche Photodiode) and by capturing Brownian motion at a single molecule level in the extremely small volume of about 1 femtoliter (1 fL = 1 x 10-15 L). Measurement time of one sample takes only a few seconds and the system allows high throughput analysis.
2. Pre-analysis sample washing not necessary.
The system can simultaneously measure, and distinguish between the fluorescent signal of both bound and free molecules when a solution is composed of both molecule types. There is no need for the vital yet troublesome sample washing steps required with previous analytical methods.
3. Solid-phased biological assay not necessary as no reliance on sensor-chips.
Simply dispensing the reacted sample into a microplate and loading the microplate into the device completes automated analysis. There is no need for the difficult preparatory step of adsorbing a solid-phased sample on the sensor chip or microplate well bottom that is required with previous analysis methods (ELISA*3 and Surface Plasmon Resonance*4).
Fluorescence Intensity Multiple Distribution Analysis. A calculation method that can measure numerous parameters (translational diffusion time*5 showing molecular size, molecular concentration, fluorescent brightness per molecule) for various types of molecules using fluorescent signal analysis.
*2 Cross-correlation Analysis:
A calculation method that analyzes fluorescent signals from molecules labeled with two different colored dyes to determine whether each colored molecule is moving individually or together. The method can measure molecular interactions more sensitively than the conventional methods.
Enzyme-linked immuno-sorbent assay. This method is described as a solid-phase enzyme immunoassay. Antigens or antibodies are labeled with enzymes and an enzyme reaction is used to detect whether antibodies or antigens are present.
*4 Surface Plasmon Resonance:
This method analyzes binding and release between two molecules, by optically detecting as an SPR signal any minute changes in mass in the study sample on the solid-phased sensor chip surface.
*5 Translational Diffusion Time:
A physical coefficient for a molecule that increases in accordance with the molecule size.
Overview of Evotec OAI AG
Address: Schnackenburgallee 114, 22525 Hamburg, Germany
President & CEO: Joern Aldag
Established: 1993
Evotec OAI offers the full range of high-value added products and services required to discover and develop drugs more effectively and efficiently based on innovative proprietary technologies. By integrating accelerated methods in biology, chemistry and screening, the Company has established a unique position as a one-stop-shop for all the critical elements in the drug discovery research and development process from gene to clinical development. More than 560 people are based in Hamburg, Germany and Abingdon, U.K. The Company's shares are listed on the Neuer Markt of the Frankfurt Stock Exchange.:
Main Specifications
Analysis Method: Single molecular fluorescence detection (FIMDA), cross-correlation analysis, and polarization analysis
Measurement Parameters: Concentration, translational diffusion time, molecular fluorescent brightness, cross-correlation, and polarization.
Laser Wavelength: 488 nm, 543 nm, 633 nm (simultaneous measurement of two wavelengths possible)
Measurement Vessel: glass-bottomed microplate (96, 384, 1536 wells/plate)
External Appearance: Bench-top device measuring W700 x H450 x D600. Externally attached laser combiner.
Automated Adjustment: Laser power, focal position, confocal pinhole, correction ring of objective lens, etc.
* The external appearance and specifications of the prototype may differ from those of the actual commercial product
*Olympus Optical Co., Ltd. was changed to OLYMPUS CORPORATION as of October 1, 2003.
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