Yokogawa Technical Report / Vol.60 No.2 (2017)

At this site technical articles published at the YOKOGAWA technical report are introduced.

Yokogawa’s Life Science Business

Preface to this Special Issue on Yokogawa’s Life Science Business

  • Masaharu Yamazaki*1

*1 : Head of Measurement Business Headquarters and Aerospace Products Business Headquarters, President of Yokogawa Test & Measurement Corporation


The World as Seen from Cells

  • Manabu Fueki*1
  • Hiroyuki Sanguu*2
  • Takayuki Kei*2, *3

*1 : Quality Assurance and Customer Support Department, Life Science Center, Measurement Business Headquarters
*2 : Business Development Center, Measurement Business Headquarters
*3 : R&D Department, Life Science Center, Measurement Business Headquarters

   Thirty years ago, Yokogawa embarked on R&D of high-speed confocal microscopes for real-time imaging of living cells and developed its first product, the CSU10 confocal scanner unit. The company then released the CellVoyager high-throughput screening system, the CQ1 all-in-one image cytometer, the CellPathfinder cell image analysis software, and other advanced products. Yokogawa is a pioneer of live cell imaging technologies and drug discovery support systems. This paper describes the technologies Yokogawa is developing for satisfying expectations in the life science field and for growing its business further.


CellVoyager CV8000: A High-throughput Cytological Discovery System for Enhancing the Efficiency of Drug Discovery

  • Yohei Tsubouchi*1
  • Mitsuru Sakashita*1
  • Tsuyoshi Nakamura*1
  • Koichi Yamamoto*1

*1 : R&D Department, Life Science Center, Measurement Business Headquarters

   Yokogawa has developed the CellVoyager CV8000 high-throughput cytological discovery system, which can elucidate the functions of individual cells or tissues composed of multiple cells by acquiring and analyzing images of cells. This system can automatically observe processes within cells caused by the administration of drug-candidate compounds, at the world’s highest resolution and measurement speed. This paper describes various functions of the CV8000, including a newly developed element technology for preserving culture environments, a water supply mechanism for water-immersion objective lenses, a digital phase contrast (DPC) technique for label-free imaging, and a function for correcting fluorescent crosstalk.


Image-processing Technologies for High Content Analysis Software

  • Koji Ohashi*1
  • Yukihiro Ina*1
  • Masahiro Araki*2
  • Hirofumi Sakashita*1

*1 : R&D Department, Life Science Center, Measurement Business Headquarters
*2 : Quality Assurance and Customer Support Department, Life Science Center, Measurement Business Headquarters

   High content analysis is an ideal method for drug discovery. It processes and analyzes images of cells and tissues, quantifies the information contained in these images, and outputs useful data. These include the count, size, shape, behavior, circumference, fluorescence intensity, localization, and speed and total distance of movement of cells. For high content analysis, Yokogawa has developed original image processing technologies. These include image data platform technology, four-dimensional image processing technology containing time and space information, and image recognition technology based on machine learning. Yokogawa has also developed the CellPathfinder analysis software using these technologies. This paper describes Yokogawa’s advanced image processing and analysis technologies.


Drug Discovery Applications of High-throughput Cytological Discovery Systems

  • Kazuyuki Sugimoto*1
  • Mahomi Suzuki*1
  • Toshinori Iwahara*1

*1 : Sales Department, Life Science Center, Measurement Business Headquarters

   Yokogawa’s range of high-throughput cytological discovery systems includes the CellVoyager CV8000 high-throughput cytological discovery system, which is a large highend type, and the CQ1 confocal quantitative image cytometer, which is a small bench-top type, both of which use the CellPathfinder high content analysis (HCA) software. By using confocal scanning technologies based on microlens-enhanced Nipkow disks, both systems can automatically acquire a large amount of high-definition, 2D/3D confocal microscopic images at high speed and quantify the information contained in these images. These systems can also provide ideal culture conditions for cells through temperature control, CO2 control, and a humidifier. These useful functions enable the systems to analyze various cellular responses and thus to be increasingly used in the drug discovery field. This paper introduces three examples of using these systems for drug discovery research: hepatotoxicity assay, cellular migration assay, and in vivo tumor metastasis assay using zebrafish.


Intracellular Substance Sampling System

  • Takayuki Kei*1, *2
  • Hironori Takai*2
  • Takuya Azuma*1
  • Kouki Nishide*2

*1 : R&D Department, Life Science Center, Measurement Business Headquarters
*2 : Business Development Center, Measurement Business Headquarters

   Intracellular substance sampling systems equipped with a nano spray tip, which is a glass capillary with a diameter of several microns, are used to develop new medicines. First, candidate drugs are administered to cells and induced reactions are detected by high content analysis (HCA). The system then aspirates substances which show expected reactions from cells, examines them by single cell mass spectrometry, and analyzes the efficacy, metabolism, and toxicity of the candidates.
   Yokogawa has developed a high-precision, high-throughput intracellular substance sampling system by combining its technologies regarding cellular image analysis, highprecision positioning, and optical design. This system makes it possible to puncture a cell and suction a specific intracellular component with one click on a PC. This cutting-edge instrument, which uses synergies of HCA and the single cell mass spectrometry method, is contributing to the advancement of life and pharmaceutical sciences. This paper describes the core technologies developed for this system and introduces the results of experiments, from intracellular substance sampling to mass spectrometry.


Applications of an Intracellular Substance Sampling System

  • Hironori Takai*1
  • Kouki Nishide*1
  • Tomoko Hirai*1

*1 : Business Development Center, Measurement Business Headquarters

   Yokogawa has developed an intracellular substance sampling system with a nano spray tip made of glass capillary. By using precise location feedback from Yokogawa’s confocal microscopy technology, this system calculates the position of the nano spray tip relative to the target cell, and thus can sample microscopic organelles accurately. In recent years, many academic papers have been published that address single-cell injection and single-cell metabolomics to identify the drug uptake of cells and localize metabolities by using mass spectrometry. However, most of them use manual procedures that require considerable skill and experience. Yokogawa’s new system can automate these procedures and can be applied to other applications such as single-cell DNA/RNA analysis and patchclamp techniques. The system also delivers added value and improves the efficiency of research and development. This paper describes applications of this system.


Development of a High-speed Super-resolution Confocal Scanner

  • Takuya Azuma*1
  • Takayuki Kei*1

*1 : R&D Department, Life Science Center, Measurement Business Headquarters

   Super-resolution microscopy techniques that overcome the spatial resolution limit of conventional light microscopy have been developed and are increasingly used for advanced research in various fields including cell biology. However, their temporal resolution is still low, so it is difficult to observe the dynamic behaviors of living cells. Furthermore, these existing techniques have restrictions on the dyes that can be used and the specimens that can be observed. Therefore, there is an increasing need for a versatile super-resolution microscopy technique that can visualize the fine structures of living cells with high temporal resolution. To meet this need, Yokogawa has developed a high-speed super-resolution confocal scanner based on its confocal scanner unit (CSU), which is proven to be ideal for observing living cells. This paper outlines the technologies implemented in this new scanner and its applications.


Image Analysis Technology for Label-free Cells

  • Hirofumi Sakashita*1

*1 : Development Department, Life Science Center, Measurement Business Headquarters

   Biological cells are essentially clear and colorless. Since their images lack contrast, it is difficult to observe them, which is why cells are usually labeled with fluorescence before analysis. However, the label-free state is a fundamental requirement for regenerative medicine. This paper introduces two technologies that help observe label-free cells more effectively. One is a digital phase contrast image for enhancing contrast, and the other is machine learning for improving recognition. We have implemented these two technologies in our CellPathfinder high content analysis software. With the assistance of a machine learning function, users can analyze images of label-free cells more precisely.


A Solution for Manufacturing Antibody Medicines

  • Tetsushi Namatame*1
  • Yukihiro Nakamura*1
  • Fumiaki Izaki*1
  • Akinari Hirano*1

*1 : Incubation Department, Innovation Center, Marketing Headquarters

   Antibody medicines are manufactured by using genetically modified animal cells. The major nutrient of cells is glucose, and so maintaining an appropriate concentration of glucose for the number and condition of cells in the culture is an effective way to increase the production of antibodies and ensure their stable quality. To improve this control, we have developed a bioreactor system consisting of three devices: (1) a near-infrared spectroscopy (NIRS) inline sensor for measuring glucose and lactate concentration, both of which are indicators of cell metabolism, (2) an impedance spectroscopy inline sensor for measuring the number of viable cells, and (3) a controller that predicts the volume of glucose consumption based on cell metabolism and automatically feeds glucose solution. We carried out an experiment with a prototype of this system and verified that it maintained glucose concentration within a set range throughout the culture period. In this paper, we describe element technologies implemented in this system and report the results of the experiment.


STARDOM Wireless I/O: A Smart Product to Unwire Small-scale Distributed Facilities

  • Kaname Kakihara*1

*1 : SCADA Business Development Department, Systems Business Division, IA Systems & Service Business Headquarters

   Yokogawa has developed STARDOM Wireless I/O, a field wireless product that is ideal for monitoring and controlling small-scale facilities distributed across wide areas. This product facilitates the introduction of a field wireless system, which complies with the ISA100.11a wireless communication standard for industrial automation, to the field quickly and at reasonable cost. Without expert knowledge of wireless network design and wireless gateway setting, users can introduce a field wireless system that complies with ISA100 Wireless and enjoy its benefits with the same time and effort as for wired instrumentation using 4–20 mA DC or other signals. This paper describes the development background, system configuration, and advantages of STARDOM Wireless I/O.


Enterprise Pipeline Management Solution

  • Takashi Yamagata*1
  • Shin-ichiro Kasahara*2

*1 : Engineering Production Technology Department, Global Project Division, IA System & Service Business Headquarters
*2 : SCADA Business Development Department, Systems Business Division, IA Systems & Service Business Headquarters

   In recent years, investment in production has been decreasing in the oil and gas industry due to a decline in crude oil prices. In contrast, capital investment in transportation is continuing to grow for ensuring efficient, reliable transportation of large quantities of oil and gas through pipelines to remote locations. This paper introduces the features and functions of the enterprise pipeline management solution (EPMS) based on FAST/TOOLS. FAST/TOOLS is a supervisory control and data acquisition (SCADA) software package for large-scale systems distributed across wide areas. The package collects, stores, and monitors data from remote terminal units (RTU) and distributed control systems (DCS).


The ADMAG TI Series Magnetic Flowmeter

  • Yuuichi Kaneko*1
  • Masakazu Saitou*1
  • Gouki Nakayama*2
  • Norio Yasuda*3
  • Daisuke Harigane*3
  • Tooru Shimura*3

*1 : Sensor Technology Department, Product Development Center, IA Products & Service Business Headquarters
*2 : Product Hardware Technology Department, Product Development Center, IA Products & Service Business Headquarters
*3 : Field Device Department, Product Business Center, IA Products & Service Business Headquarters

   Yokogawa has developed the ADMAG Total Insight (TI) series magnetic flowmeter. Under the new Total Insight concept, Yokogawa supports the magnetic flowmeters of this series throughout their lifecycle. Currently, the AXG model and the AXW model are available for various applications. Their ease of maintenance has been improved by increased resistance to vibrations and an enhanced diagnosis function required for steady operations and maintenance. This paper describes the core technologies implemented in the ADMAG TI series magnetic flowmeter.


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