The Development of Hemoglobin A1c (HbA1c)
fractionation quantitative analyzer
In the summer of 1979, a development
theme for a new instrument was determined, and a team
of 6 - 7 engineers of machines, electronics, and software
was organized. The theme was to develop a testing
instrument using hemoglobin A1c (HbA1c) analytical
column, which was a collaborative project of Sekisui
Chemical Co., Ltd Central Research Institute and Osaka
City University Medical School. In those days, it
was not practical to measure HbA1c because the hemoglobin
analyzer was too expensive and difficult to use, and
it took as long as 24 hours for measuring. The goal
for the development team was producing a single-analyte
hemoglobin analyzer which could be operated even by
a lay user on a daily basis.
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The world first Hemoglogin
A1c analyzer (AUTO A1c)
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Hemoglobin A1c and High Performance Liquid
Chromatography (HPLC) Method
HbA1c, a type of glycated protein, is a binding of hemoglobin
(protein) and glucose (sugar). HbA1c accounts for about
4 to 15 % of total hemoglobin. Since HbA1c represents the
average blood glucose level of the past 2 weeks, it is an
indispensable test item for diabetes diagnosis and care.
Measuring HbA1c requires fractionating hemoglobin into various
different types of hemoglobin for quantification where the
proportion of the different hemoglobin is calculated. Liquid
Chromatography (LC) method was typically used for this.
Liquid chromatography has a long history.
It is said that it was originated in a discovery by
a Russian botanist. The Russian botanist Mikhail S.
Tswett (1872-1919) found that pigment
composition became separated when plant pigment (chlorophyll)
together with petroleum ether went through calcium
carbonate layer. High Performance Liquid Chromatography
(HPLC), which is faster liquid chromatography, is
now the necessity in separation analysis.
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Mikhail S. Tswett
(1872-1919)
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When the new analyzer was being developed, HPLC instruments
were on the market as general-purpose instruments. However,
they were used only in university laboratories, professional
analysis companies, and some test institutions, because
they were huge and complicated system that required expert
operators to keep stable use condition. In addition, even
small changes in flow volume, pressure, temperature, and
chromatography column would cause a big difference in the
test result, so that people believed that HPLC was not suitable
for quantitative analysis in clinical settings.
Under the situation, our company's engineers worked hard
on what would make it possible to bring in HPLC to clinical
fields.
They came to the conclusion that the key was the performance
stability and the price of the system. In HPLC, the solution
sending pressure sometimes goes up to 50Kg/cm2 or more
(the same pressure you get in 500m water depth), so the
new analyzer needed many unusual components that were
most unlikely in ordinary automatic biochemical test instrument
(such as high-pressure solution sending pump, high-pressure
bulb, high-pressure damper etc). If we had bought all
of these components, it would have cost us tens of millions
of yen. Thus, we decided to make the components in our
company, making the best of all the HPLC techniques that
had been developed until then. Most of the technical challenges
were totally new for our development team -- development
of flow cell optical system with small dead volume and
good linearity, high-pressure pump with little pulse,
high-pressure injection bulb, floating point calculation
software with wide dynamic range, control of new microcomputer
system, etc. We achieved them one by one, and made high-quality
and low-price components, and finally succeeded in developing
a HPLC system for high performance at reasonable price
that could be accepted by general hospitals and test institutions.
Our company took charge of the development of the instruments
and Sekisui Chemical took charge of the development of
the chromatography column. Together we gave birth to HA-8110,
the world's first HPLC HbA1c fractionation quantitative
analyzer.
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