Principles of Enzyme Thermistor Systems: Applications to Biomedical and Other Measurements - Advances in Biochemical Engineering Biotechnology - page 3

attention in the area of biosensors and has been successfully exploited in the last
two decades.The initial biosensing applications focused on the determination of
glucose and urea, and has subsequently been applied in the determination of a
wide variety of molecules [3].
Development of simple, low-cost calorimeters for routine analysis, called
thermal enzyme probes (TEP), has been attempted by several groups. These are
fabricated by attaching the enzyme directly to a thermistor [4, 5]. However, in
this configuration, most of the heat evolved in the enzymic reaction is lost to the
surrounding, resulting in lower sensitivity. The concept of TEP was essentially
designed for batch operation, in which the enzyme is attached to a thin alumi-
num foil placed on the surface of the Peltier element that acts as a temperature
sensor [6].
Although in later designs [7, 8], the sensitivity of TEP was improved, con-
siderable enhancement in detection efficiency was achieved by employing a
small column, with the enzyme immobilized on a suitable support. In this case,
the heat is transported by the circulating liquid passing through the column to
a temperature sensor mounted at the top of the column. Several models of this
configuration were developed in the mid-1970s, including the enzyme thermi-
stor and the immobilized enzyme flow - enthalpimetric analyzer [9, 10]. Further-
more, a commercial flow-enthalpimeter combined with an immobilized enzyme
column has also been described [11].
Recently, several miniaturized prototypes have been fabricated, e.g., a thermal
probe for glucose, designed as an integrated circuit, called a biocalorimetric
sensor, with total dimensions of only 1

0.3 mm [12]. In a different model, a
small thermoelectric glucose sensor employing a thin-film thermopile to mea-
sure the evolved heat was described.These devices were reported to be less affect-
ed by external thermal effects compared to thermistor based calorimetric sen-
sors and could be operated without environmental temperature control [13].
Active work is in progress in the authors' laboratory to construct a miniaturized
portable biothermal flow-injection system suitable for on-line monitoring. An
instrument with 0.1-0.2 mm (ID) flow channels and a flow rate of 25-30

¥ 1 ¥

m l/min

with sample volumes of 1-10 5 mm enzyme

column allows determination of glucose concentrations down to 0.1 mM.Recent-
ly a device equipped with thin-film temperature sensors of thermistor type (0.1

m l is being evaluated at present. A 1 ¥

¥

0.1 mm or smaller) for glucose measurements has also been developed [14].

1.2
Principle of Calorimetric Measurement

The total heat evolution is proportional to the molar enthalpy and to the total
number of product molecules created in the reaction.
Q=-n p (

H)
where Q = total heat, n p =moles of product,and

D

H = molar enthalpy change. It
is also dependent on the heat capacity C p of the system, including the solvent:
Q=C p (

D

D T)