Microcantilever based disposable viscosity sensor for serum and blood plasma measurements

Abstract

a b s t r a c tThis paper proposes a novel method for measuring blood plasma and serum viscosity with a microcantilever-based MEMS sensor. MEMS cantilevers are made of electroplated nickel and actuated remotely with magnetic field using an electro-coil. Real-time monitoring of cantilever resonant frequency is performed remotely using diffraction gratings fabricated at the tip of the dynamic cantilevers. Only few nanometer cantilever deflection is sufficient due to interferometric sensitivity of the readout. The resonant frequency of the cantilever is tracked with a phase lock loop (PLL) control circuit. The viscosities of liquid samples are obtained through the measurement of the cantilever's frequency change with respect to a reference measurement taken within a liquid of known viscosity. We performed measurements with glycerol solutions at different temperatures and validated the repeatability of the system by comparing with a reference commercial viscometer. Experimental results are compared with the theoretical predictions based on Sader's theory and agreed reasonably well. Afterwards viscosities of different Fetal Bovine Serum and Bovine Serum Albumin mixtures are measured both at 23°C and 37°C, body temperature. Finally the viscosities of human blood plasma samples taken from healthy donors are measured. The proposed method is capable of measuring viscosities from 0.86 cP to 3.02 cP, which covers human blood plasma viscosity range, with a resolution better than 0.04 cP. The sample volume requirement is less than 150 ll and can be reduced significantly with optimized cartridge design. Both the actuation and sensing are carried out remotely, which allows for disposable sensor cartridges.

A cartridge based sensor array platform for multiple coagulation measurements from plasma

“…In our previous studies, we conducted blood plasma viscosity measurements through phase measurements with high sensitivity using the proposed scheme 21,22 . During blood coagulation, a sudden change in the blood plasma viscosity occurs due to fibrin generation 13 .…”

“…The PMMA cartridge contains the MEMS dies with 2.5mm x 2.5 mm size. The nickel cantilevers are actuated magnetically with a coil placed in close proximity of the backside of the PMMA flow cell 21 . The coil is driven with a high power broadband current amplifier.…”

“…Optical measurement techniques based on grating interferometer, and knife-edge methods have also been successfully implemented in our group. Therefore, the LDV can be changed with other techniques to provide measurement parallelism 21,25 . The phase difference between the coil drive and LDV is monitored with a Lock-in Amplifier (Zurich Instruments HF2LI) and recorded simultaneously using a Labview interface.…”

“…In our previous works we measured the viscosity changes with a sensitivity of 0.01 cP, by tracking frequency at constant phase difference 21 or by tracking phase changes at constant frequency 22 . During blood coagulation a sudden change in blood plasma viscosity occurs.…”

“…This is due to the higher viscosity and density of blood plasma with respect to DI water. Detailed information can be obtained from our previous studies on blood plasma viscosity 21,22 . During blood coagulation, a sudden change in the blood plasma viscosity occurs due to fibrin generation 13 .…”