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Academia Sinica E-news No.191
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A Chip That Tells More Sweet Findings
 

The “Sugar Array” team in the Genomics Research Center at Academia Sinica has been devoted to the development of ingenious resolutions targeting glycan-related issues. Led by Dr. Chung-Yi Wu and Dr. Chi-Huey Wong, the team has recently published two of their innovative approaches regarding Sugar Array technology in the “Journal of the American Chemical Society”. The same team had published its first solution for cancer detection back in 2008. Now, it has moved on to the detection of influenza types, as well as selecting enzyme candidates for developing biomass energy.

The fundamental mechanism of Sugar Arrays is to design, make, and arrange various glycosylated molecules on a tiny glass chip, and then, by observing their binding with the substance applied on the chip, ascertain the identity of the substance.

        Globalization has changed the pace and scope of our lives, making contagious diseases travel faster and farther as well. With the appearance of SARS, H5N1 type avian flu, H1N1 flu, and new antibiotic-resistant germs one after another, it is inevitable that we not only need to be able to cure, but also be equipped with better and faster tools to prevent epidemics.

In a three-year effort in designing a chip for diagnosing influenza, the team first obtained various types of the virus strains with help from the Center of Disease Control. With their specialized training in glycoscience, the GRC team were able to design and synthesize glycans that bind the hemagglutinin molecules found on various influenza viral surfaces. As a result, they planted 17 such glycans that bind avian viruses and 10 that bind human viruses on the chip.

The research result shows that by applying the infected saliva on the chip, then reading by a fluorescence reader, one could pinpoint clearly in a matter of minutes whether the viral infection is of type A, type B, a new H1N1 type, or a rare avian flu that usually only infects birds. So far, a so-called “rapid test method” being used in the clinics can only distinguish if the infection is type A, or not type A. 

“What’s scary about the influenza virus is that it is an RNA type virus, which means, when it mutates, there is no way to amend in nature’s way, so the mutation simply goes on and on”, explained Dr. Wu. However, he added that “with our sugar flu chip, we can establish a pattern for any new kind of flu in a rapid manner, thus, take adequate measurement in the fastest time frame”.

When asked about the plan to transfer this technology into a product, Wu hinted that some biotech companies have expressed interest in the technology.

This research has been published online at the JACS website (http://pubs.acs.org/doi/pdf/10.1021/ja104657b). Other contributors include Dr. Winston Chen, Dr. Ting-Jen Cheng, Dr. Jia-Tsrong Jan, Dr. Chien-Tai Ren, Dr. Chi-Hui Liang, and doctoral students Hsin-Yu Liao and Che-Hsiung Hsu.

Another application of the Sugar Arrays was published on JACS earlier as well (http://pubs.acs.org/doi/pdf/10.1021/ja1046523 ), in which the team not only made improvements in the chip material, but also demonstrated its usefulness by collaborating with a Biomass energy research team in Academia Sinica.

The transparent nature of the glass chip makes the handling more difficult. This entails a problem for quality control should it one day reach the production line. Therefore, the team devised a method to coat a thin layer of aluminum oxide on the glass slide and attach a sugar covalently to the aluminum surface through a spacer group. When characterized by a mass spectrometer, the laser beam from the mass spectrometer will cleave the cleavable bond and release the sugar.

By working with the Biomass team to study its effectiveness in analyzing various cellulase activities,the team proved this sugar chip approach can improve their efficiency dramatically.

In addition to Dr. Chung-Yi Wu, an Assistant Research Fellow of the Genomics Research Center, and Dr. Chi-Huey Wong, currently the President of Academia Sinica, major participants of these projects are: Dr. Andrew Wang, Vice President of Academia Sinica, and postdoctoral fellows Dr. Susan Tseng, Dr. Jeng-Liang Han, Dr. Wen-Yih Jeng, and doctoral students Shih-Huang Chang, Hsin-Yu Lee, and Chin-Wei Lin.

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