Page 414 - Handbook of Biomechatronics

The Artificial Pancreas 409

North American market. The Toronto group called their substance insulin
and Eli Lilly called their product iletin (Leiva-Hidalgo et al., 2011).

3 BLOOD SUGAR MONITORING
In 1841, Karl Trommer developed a qualitative test for sugar, which
involved treating a urine sample with a strong acid that resulted in the con-
version of disaccharides into monosaccharides. This solution was then neu-
tralized and a solution of copper sulfate and further alkali added. After
boiling, a brick-red cuprous oxide precipitate formed if glucose was present.
A decade later Hermann von Fehling developed a qualitative test based on
this work (Kirchhof et al., 2008).
The first semiquantitative urine glucose test was devised in 1907 by Stan-
ley Benedict and this remained the only method to monitor glucose levels in
diabetic patients for many years. By 1925 home testing for glucose in urine
was possible using Benedict’s reagent generally provided by the family doc-
tor. The principle of Benedict’s test is that when reducing sugars are heated
in the presence of an alkali they are converted to powerful reducing agents
called enediols. In turn, these reduce the cupric compounds (Cu 2+) present
+
in the reagent to cuprous compounds (Cu ) which precipitate as insoluble
copper oxide (Cu 2 O). The color of the precipitate provides a reasonably
quantitative indication of the glucose concentration.
3
In the home tests, eight drops of urine were mixed with 6cm of Ben-
edict’s reagent in a test tube. The tube was placed in boiling water for 5min
after which a color change occurred and a color chart could be used to deter-
mine the amount of glucose present. A greenish color indicated a small
amount of sugar, while increasing sugar concentrations were indicated by
yellow (moderate) and finally red/orange precipitates indicating a high con-
centration. This test process was later simplified by providing an effervescent
tablet that could be dropped into a test tube containing urine. By 1956 dry
test strips using the glucose oxidase (GOx) method had become available
(Bronzino, 2006).
The measurement of glucose in urine is not a satisfactory method for the
control of diabetes as only after the blood glucose level has been high for a
number of hours does it spill over into the urine.
Initially, testing for glucose in blood required large volumes of the liquid.
However, micromethods initially developed by Ivar Bang and soon
improved by Lewis and Benedict in 1915 and in 1918 by Hagedorn and
Jensen became available. Bang’s test functioned by fixing blood proteins