Microfluidic chips for the measurement of calcification propensity

RWTH Publications (RWTH Aachen), vol. 90, pp. 1326–1327

Abstract

Kidney stones, bladder stones and calcium deposits in coronary vessels or in the brain are examples of pathological calcification. The propensity of patients to suffer from such pathological calcification is measured by adding calcium and phosphate to blood serum and measuring the time until turbidity occurs due to the formation of calciprotein particles (CPP). The time of this transformation is called T50 and correlates with the calcification propensity of a patient. The T50 test takes into account all the parameters involved in the calcification and thus allows a better diagnosis than a Fetuin-A or phosphate concentration measurement. Conventional measuring methods for the T50 time, such as e.g. nephelometry are relatively complex and lengthy. The objective of this work was to investigate whether a reproducible T50 measurement can be achieved in a few minutes. Thus, an alternative measurement setup with disposable microchips has been further developed. It is based on the measurement of the CPP conversion time, either electrochemically by means of impedance spectroscopy, or by means of laser and photo resistor. Microstructured polymer chips were developed, of which about 1200 pieces were produced. Each of these polymer chips contains a cuvette in which the CPP conversion in a mixture of blood serum with calcium and phosphate is measured. The T50 is recognized by the level in the turbidity of the serum samples or their electrical alternating current resistance. The best of the electrode designs for impedance spectroscopy tested is the one with two rod electrodes in the cuvette. The measurements can be carried out with serum, plasma and heparinized whole blood, but did not lead to reproducible results. For the optical measurement-set-up, the signal-to-noise ratio was significantly improved by extending the light path through the mixed educts by mirror surfaces in the cuvette. The measuring time was shortened to a few minutes by raising the temperature of the chip to up to 85 °C via a controllable Peltier element integrated in the measuring setup. A linear correlation of the T50 times measured in the nephelometer at 37 °C and in the microchip at 75 °C, shows that the measurement with the microchip-based test method in less than 10 minutes with a low coefficient of variance of about 6 % is possible. A medical validation with a sufficiently large number of test individuals now became possible.

Authors 1

1. Julia Bavendiek corresponding Aachen

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen

   RWTH Aachen; Lehr- und Forschungsgebiet Konstruktion und Entwicklung von Mikrosystemen (KEmikro); Campus-Boulevard 30 52074 Aachen Deutschland