Sensors and Actuators A 110 (2004) 33–38
Biological microsystem for measuring uric acid in biological fluids
G. Minas
a,∗
, J.S. Martins
a
, J.C. Ribeiro
a
, R.F. Wolffenbuttel
b
, J.H. Correia
a
a
Department of Industrial Electronics, University of Minho, Campus de Azurém, 4800-058 Guimarães, Portugal
b
Fac. ITS Dept. Microelectronics, Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands
Received 25 September 2002; received in revised form 26 September 2003; accepted 10 October 2003
Abstract
This paper describes a biological microsystem (bio-system) for measuring uric acid concentration in serum, plasma or urine. Its operation
is based on optical absorption in a well-defined part of the visible spectrum. The bio-system is composed by two dies: one is fabricated
in polystyrene and contains the microchannels and the other is fabricated in a CMOS standard process and contains the photodetector and
readout electronics. The uric acid concentration is measured by using a mixture of 14 l of infinity
TM
uric acid reagent with 0.25 l of
sample. The achieved sensitivity is 0.33 mg/dl (±0.6% of the value in urine of a healthy person), with a 1 mm lightpath. Using an optical
absorption method, a maximum peak at wavelength λ = 494 nm, is detected. This bio-system can be included in the group of low-cost
disposable devices for biological fluids analysis.
© 2003 Elsevier B.V. All rights reserved.
Keywords: Bio-system; Uric acid; Optical absorption
1. Introduction
Over the past decade, the miniaturization of fluidic analy-
ses systems has become a highly visible and dominant trend
in physical and biological sciences [1]. Presently, disease
prevention and treatment is often based on the measurement
of chemical parameters in biological samples, such as blood
and urine. In most cases, the samples need to be sent to
a central laboratory for analysis, and the results of routine
tests become available after several hours, sometimes days.
Apart from the time delay, also the mistakes in the logistics,
such as lost samples and mislabeling, may hamper timely
diagnosis. Therefore, development in miniaturization of flu-
idic analyses systems has been driven by a need for rapid,
on-line measurements with low concentrations and low sam-
ples volumes, which is essential within fields such as DNA
analysis, drug discovery, pharmaceutical screening, medical
diagnostics, environmental analysis and chemical produc-
tion. The advantages associated with shrinking analytical
systems include improved efficiency with respect to sam-
ple size, response times, costs, analytical performance, inte-
gration, throughput, automation, and laboratory safety [2].
Keywords in this field are “bio-system”, “lab-on-a-chip” or
∗
Corresponding author. Tel.: +351-253510190; fax: +351-253510189.
E-mail address: gminas@dei.uminho.pt (G. Minas).
“TAS” (micro total analysis system), where macroscopic
analysis methods are being miniaturized.
Microscale fluidic systems have distinctive properties as
a result of their small dimensions. First of all, liquid flow is
generally laminar, not turbulent. Secondly, diffusion in nar-
row channels is practically the only process for mixing flu-
ids, and thirdly, particles can also be separated by diffusion
according to their size [3]. In system signal processing and
data pre-handling, the small size and low power consump-
tion of such highly integrated systems could make them
highly portable and thus suitable for in situ measurements
tasks. The application of the particular bio-system presented
here is the measurement of uric acid concentration in human
being’s urine.
1.1. Background of the uric acid analysis
Uric acid is a metabolite of purines, nucleic acids and
nucleoproteins. Consequently, abnormal levels may be in-
dicative of a disorder in the metabolism of these substances.
Hyperuricaemia may be observed in renal dysfunction,
gout, leukemia, polycythaemia, atherosclerosis, diabetes,
hypothyroidism, or in some genetic diseases. Decreased
levels are present in patients with Wilson’s disease. A nor-
mal adult synthesizes 26.9–53.8 mg/dl of uric acid in urine.
In case of disease, these values can be as low as 17 mg/dl
or too high up to 67 mg/dl [4].
0924-4247/$ – see front matter © 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.sna.2003.10.049