Support for early-stage disease detection by nanotech applications

Early-stage detection and treatment of diseases is of the greatest importance in the clinical environment. Various tests are now performed for early-stage identification of the causes of diseases, but work to increase the precision, and ease of performance, of such tests is far from complete.

In 2004, Furukawa Electric Co., Ltd. established its Bio-Team, within the Research and Development Division. The groundwork for the Bio-Team had already been laid, as technology relating to molecular-level analysis and control, developed over many years, including copper alloys, plastics for use as insulators for electric wiring, and glass-based materials for use in optical fibers. After establishment of the Bio-Team, work on nanotechnological bio-products was started in earnest, and this led to success in the form of development of Quartz Dot®, which consists of fluorescent silica nanoparticles formed by enclosing fluorescent pigments inside silica nanoparticles at high density. The aim is to apply Quartz Dot to assay agents, and work is being continued on establishing this as a unique technology.

The structure of Quartz Dot, in terms of the arrangement of functional groups, is such that antibodies and other biomolecules bind readily to the particle surfaces. In addition, depending upon the application, particle diameters can be set precisely over the 50 to 400 nm range. By application of these particles to immunochromatographic assay agents, it is hoped that it will be possible to achieve more sensitive diagnoses than have been possible to date.

Immunochromatography is a simple diagnostic method that has now been in general use for a considerable time, and is widely used for diagnosis of diseases such as influenza. A biological sample such as saliva is dripped on one end of a diagnostic kit, and the diagnosis is made on the basis of color changes that occur as a result of binding with antibodies contained in the sample.

1. A biological sample such as saliva is dripped on one end of the diagnostic kit.


2. The test substance, contained in the biological sample, undergoes an antigen-antibody reaction with the nanoparticle, resulting in binding.


3. The nanoparticles to which the test substance is bound move on a membrane, as a result of the capillary phenomenon.


4. Antibodies that are fixed on the membrane in a linear configuration, and the nanoparticles to which the test substance is bound, undergo a secondary antigen-antiparticle reaction.


5. By accumulation in a linear configuration, the nanoparticles form a colored line.


6. The colored line can be confirmed visually, and judgment is made on that basis.

In most of the techniques in previous use, colorization is observed under natural light. With Quartz Dot, on the other hand, diagnosis is made on the basis of observation of fluorescence generated by illumination with light of a specific wavelength. Quartz Dot thus has very high sensitivity, enabling diagnosis even when the antibody content is such that it would not be detectible by the techniques in previous use. In the case of Campylobacter, for example, detection with the colorization-type assay agents in previous use required at least 10,000 bacteria, whereas with fluorescence immunochromatographic assay agents using Quartz Dot, stable detection is possible with just 200 bacteria. This improvement in sensitivity enables earlier-stage detection of diseases, and it is hoped that this will make a major contribution to disease treatment.

By modifying antibodies on the surface of Quartz Dot, various antibodies, such as those of influenza viruses and noroviruses, can be detected, and research and development of assay agents is currently being carried out in collaboration with external organizations, as detailed below.

• Acanthamoeba ophthalmologic infections (release date: July 9, 2013):
  
  "Successful Development of World's First High-sensitivity Immunochromatographic Test Kit Using Fluorescent Silica Nanoparticle"
  (collaborative research and development with Professor Yuichi Ohashi, Dept. of Ophthalmology, Ehime University School of Medicine.)



• Campylobacter (release date: March 17, 2015):
  
  "A new test agent for detecting bacteria in meat products and preventing food poisoning"
  (collaborative development with Osaka Prefectural Institute of Public Health).



• Amebic dysentery (release date: March 18, 2016):
  
  "New Examination Drug for Infection Detection and Reduction of Burden of Antibody Test Reagent Introduction"
  (collaborative development with Professor Hiroshi Tachibana, Tokai University School of Medicine).

The initial commercial launch was in October 2015, by Furukawa Electric Advanced Engineering Co., Ltd. (Furukawa AE), which is our group company based in Ichihara, Chiba Prefecture (CEO: Hiromi Hirono). In connection with commercialization, Hideki Watanabe, of Furukawa AE, has this to say:

Furukawa AE is an original equipment manufacturer, providing various types of product that are applied to dispensing devices, including those used in the medical field, and we have a great deal of experience of developing life-science-related products. We also have experience of developing devices that involve application of fluorescence observation, and in our current projects we are collaboratively developing fluorescence immunochromatoscopes and quantitative readers.For commercialization of Quartz Dot, also, we have sought advice and help, on the basis of the strong background we already have in this field, from personnel in various departments, especially the Electrical Engineering Production Technology Dept., in relation to issues such as aggressive approaches to new business areas, stabilization of production processes, and marketing, and our position is now established on that basis. At the present time, we are having evaluations as a reagent performed by various companies and contract research organizations, but, at any rate, on the basis of the feedback we have received about the high sensitivity of the product, we look forward to major commercial growth. In future, we hope to develop and use unique and specific fluorescent pigments, and thus expand our product line-up, and we consider that the high sensitivity and ease of use of Quartz Dot constitute a major appeal for it as a commercial product.

In addition, with respect to research and development, Kazutomi Miyoshi, of the Advanced Technology Institute, has the following to say about his hopes for increasing the speed of pioneering new business fields by our company:

Our company, as a materials manufacturer, has great potential for technological development in fields such as superconductors and nanotechnology. Issues that are important in the current development of Quartz Dot are the degrees to which silica particle diameters can be controlled, to which fluorescent pigments can be stably enclosed inside silica particles, and to which particle surfaces can be treated in an appropriate manner. A large quantity of data has been accumulated in order to resolve these issues. Technology for nanoscale control is an important and essential factor in the fundamentals of the new commercial areas that our company is targeting. In future, we will continue to aim for new technological development, and to tackle it energetically.